Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers
Identifieur interne : 000817 ( Pmc/Curation ); précédent : 000816; suivant : 000818Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers
Auteurs : Xiaomei Yang ; Jing Zhao ; Siliang Duan ; Xiaoqiong Hou ; Xi Li ; Zixi Hu ; Zhuoran Tang ; Fengzhen Mo ; Xiaoling LuSource :
- Theranostics [ 1838-7640 ] ; 2019.
Abstract
Url:
DOI: 10.7150/thno.33383
PubMed: 31281532
PubMed Central: 6592167
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers</title><author><name sortKey="Yang, Xiaomei" sort="Yang, Xiaomei" uniqKey="Yang X" first="Xiaomei" last="Yang">Xiaomei Yang</name></author><author><name sortKey="Zhao, Jing" sort="Zhao, Jing" uniqKey="Zhao J" first="Jing" last="Zhao">Jing Zhao</name></author><author><name sortKey="Duan, Siliang" sort="Duan, Siliang" uniqKey="Duan S" first="Siliang" last="Duan">Siliang Duan</name></author><author><name sortKey="Hou, Xiaoqiong" sort="Hou, Xiaoqiong" uniqKey="Hou X" first="Xiaoqiong" last="Hou">Xiaoqiong Hou</name></author><author><name sortKey="Li, Xi" sort="Li, Xi" uniqKey="Li X" first="Xi" last="Li">Xi Li</name></author><author><name sortKey="Hu, Zixi" sort="Hu, Zixi" uniqKey="Hu Z" first="Zixi" last="Hu">Zixi Hu</name></author><author><name sortKey="Tang, Zhuoran" sort="Tang, Zhuoran" uniqKey="Tang Z" first="Zhuoran" last="Tang">Zhuoran Tang</name></author><author><name sortKey="Mo, Fengzhen" sort="Mo, Fengzhen" uniqKey="Mo F" first="Fengzhen" last="Mo">Fengzhen Mo</name></author><author><name sortKey="Lu, Xiaoling" sort="Lu, Xiaoling" uniqKey="Lu X" first="Xiaoling" last="Lu">Xiaoling Lu</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31281532</idno><idno type="pmc">6592167</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592167</idno><idno type="RBID">PMC:6592167</idno><idno type="doi">10.7150/thno.33383</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000817</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000817</idno><idno type="wicri:Area/Pmc/Curation">000817</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000817</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers</title><author><name sortKey="Yang, Xiaomei" sort="Yang, Xiaomei" uniqKey="Yang X" first="Xiaomei" last="Yang">Xiaomei Yang</name></author><author><name sortKey="Zhao, Jing" sort="Zhao, Jing" uniqKey="Zhao J" first="Jing" last="Zhao">Jing Zhao</name></author><author><name sortKey="Duan, Siliang" sort="Duan, Siliang" uniqKey="Duan S" first="Siliang" last="Duan">Siliang Duan</name></author><author><name sortKey="Hou, Xiaoqiong" sort="Hou, Xiaoqiong" uniqKey="Hou X" first="Xiaoqiong" last="Hou">Xiaoqiong Hou</name></author><author><name sortKey="Li, Xi" sort="Li, Xi" uniqKey="Li X" first="Xi" last="Li">Xi Li</name></author><author><name sortKey="Hu, Zixi" sort="Hu, Zixi" uniqKey="Hu Z" first="Zixi" last="Hu">Zixi Hu</name></author><author><name sortKey="Tang, Zhuoran" sort="Tang, Zhuoran" uniqKey="Tang Z" first="Zhuoran" last="Tang">Zhuoran Tang</name></author><author><name sortKey="Mo, Fengzhen" sort="Mo, Fengzhen" uniqKey="Mo F" first="Fengzhen" last="Mo">Fengzhen Mo</name></author><author><name sortKey="Lu, Xiaoling" sort="Lu, Xiaoling" uniqKey="Lu X" first="Xiaoling" last="Lu">Xiaoling Lu</name></author></analytic><series><title level="j">Theranostics</title><idno type="eISSN">1838-7640</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background</bold>: Adequate recruitment of highly active tumor antigen-specific cytotoxic T lymphocytes (CTLs) remains a major challenge in cancer immunotherapy.</p><p><bold>Objective</bold>: To construct liposome (LP)-based nanocapsules with surface endoglin aptamer (ENG-Apt) encapsulating mouse interferon-inducible protein-10 (mIP-10), with the ability to target mouse tumor vascular endothelial cells (mTECs) and enhance CTLs targeting and recruitment to the tumor vasculature.</p><p><bold>Methods</bold>: ENG-Apt/mIP-10-LP nanocapsules were prepared by grafting DSPE-PEG<sub>2000</sub>-ENG-Apt on the surface of liposomes containing mIP-10 plasmids, characterized and assessed for the cell binding specificity<italic> in vitro</italic>. The tumor-targeting ability of ENG-Apt/mIP-10-LP nanocapsules was evaluated<italic> in vivo</italic>. The anti-tumor efficacy of ENG-Apt/mIP-10-LP nanocapsules treatment, as well as the combination treatment of ENG-Apt/mIP-10-LP nanocapsules and adoptive TRP2CD8<sup>+</sup> T cells, were both tested in melanoma-bearing mice, by evaluation of the tumor volume and the mouse survival time. To discuss the anti-tumoral mechanism of ENG-Apt/mIP-10-LP nanocapsules-based therapies, IFN-γ secretion, proportion of TRP2CD8<sup>+</sup> T cells among TILs, MDSCs in the tumor microenvironment and Tregs in the spleen, were determined after the treatments. Proliferation and apoptosis of tumor cells, and tumor angiogenesis were also assessed.</p><p><bold>Results</bold>: The prepared ENG-Apt/mIP-10-LP nanocapsules possess an adequate nanometric size, good stability, high specificity to mTECs and tumor sites, along with the ability to induce mIP-10 expression <italic>in vitro</italic> and<italic> in vivo</italic>. Treatment of ENG-Apt/mIP-10-LP nanocapsules demonstrated CTLs enrichment into the tumor site, which inhibited tumor cell proliferation and angiogenesis, as well as promoted tumor-cell apoptosis, leading to a decrease in tumor progression and prolonged survival time in melanoma tumor-bearing mice. In addition, the proportion of MDSCs and Tregs was found to decrease. The combination of ENG-Apt/mIP-10-LP nanocapsules with adoptive TRP2CD8<sup>+</sup> T cells, showed stronger abilities in inhibiting tumor growth and increasing animal survival time, thereby displayed an enhanced anti-melanoma tumor efficacy, due to the recruitment of both endogenous CD8<sup>+</sup> T cells and exogenous TRP2CD8<sup>+</sup> T cells <italic>in vivo</italic>.</p><p><bold>Conclusion</bold>: ENG-Apt/mIP-10-LP nanocapsules could enhance the recruitment of both endogenous and exogenous CTLs specifically targeting melanoma tumor vasculatures and exert anti-tumoral effect, therefore provides a potentially novel strategy for tumor immunotherapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Koning, D" uniqKey="Koning D">D Koning</name></author><author><name sortKey="Costa, Ai" uniqKey="Costa A">AI Costa</name></author><author><name sortKey="Hasrat, R" uniqKey="Hasrat R">R Hasrat</name></author><author><name sortKey="Grady, Bp" uniqKey="Grady B">BP Grady</name></author><author><name sortKey="Spijkers, S" uniqKey="Spijkers S">S Spijkers</name></author><author><name sortKey="Nanlohy, N" uniqKey="Nanlohy N">N Nanlohy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fernandez, I" uniqKey="Fernandez I">I Fernandez</name></author><author><name sortKey="Ooi, Tp" uniqKey="Ooi T">TP Ooi</name></author><author><name sortKey="Roy, K" uniqKey="Roy K">K Roy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Newell, Ew" uniqKey="Newell E">EW Newell</name></author><author><name sortKey="Lin, W" uniqKey="Lin W">W Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerdemann, U" uniqKey="Gerdemann U">U Gerdemann</name></author><author><name sortKey="Vera, Jf" uniqKey="Vera J">JF Vera</name></author><author><name sortKey="Rooney, Cm" uniqKey="Rooney C">CM Rooney</name></author><author><name sortKey="Leen, Am" uniqKey="Leen A">AM Leen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiu, Yl" uniqKey="Chiu Y">YL Chiu</name></author><author><name sortKey="Schneck, Jp" uniqKey="Schneck J">JP Schneck</name></author><author><name sortKey="Oelke, M" uniqKey="Oelke M">M Oelke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garrido, F" uniqKey="Garrido F">F Garrido</name></author><author><name sortKey="Perea, F" uniqKey="Perea F">F Perea</name></author><author><name sortKey="Bernal, M" uniqKey="Bernal M">M Bernal</name></author><author><name sortKey="Sanchez Palencia, A" uniqKey="Sanchez Palencia A">A Sánchez-Palencia</name></author><author><name sortKey="Aptsiauri, N" uniqKey="Aptsiauri N">N Aptsiauri</name></author><author><name sortKey="Ruiz Cabello, F" uniqKey="Ruiz Cabello F">F Ruiz-Cabello</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ribatti, D" uniqKey="Ribatti D">D Ribatti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhuo, H" uniqKey="Zhuo H">H Zhuo</name></author><author><name sortKey="Peng, Y" uniqKey="Peng Y">Y Peng</name></author><author><name sortKey="Yao, Q" uniqKey="Yao Q">Q Yao</name></author><author><name sortKey="Zhou, N" uniqKey="Zhou N">N Zhou</name></author><author><name sortKey="Zhou, S" uniqKey="Zhou S">S Zhou</name></author><author><name sortKey="He, J" uniqKey="He J">J He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Richmond, A" uniqKey="Richmond A">A Richmond</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagpal, Ml" uniqKey="Nagpal M">ML Nagpal</name></author><author><name sortKey="Davis, J" uniqKey="Davis J">J Davis</name></author><author><name sortKey="Lin, T" uniqKey="Lin T">T Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Zhang, Fc" uniqKey="Zhang F">FC Zhang</name></author><author><name sortKey="Zhao, Hy" uniqKey="Zhao H">HY Zhao</name></author><author><name sortKey="Lu, Xl" uniqKey="Lu X">XL Lu</name></author><author><name sortKey="Sun, Y" uniqKey="Sun Y">Y Sun</name></author><author><name sortKey="Xiong, Zy" uniqKey="Xiong Z">ZY Xiong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, Xl" uniqKey="Lu X">XL Lu</name></author><author><name sortKey="Jiang, Xb" uniqKey="Jiang X">XB Jiang</name></author><author><name sortKey="Liu, Re" uniqKey="Liu R">RE Liu</name></author><author><name sortKey="Zhang, Sm" uniqKey="Zhang S">SM Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagpal, Ml" uniqKey="Nagpal M">ML Nagpal</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Lin, T" uniqKey="Lin T">T Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Zhao, Lm" uniqKey="Zhao L">LM Zhao</name></author><author><name sortKey="Zhao, Xl" uniqKey="Zhao X">XL Zhao</name></author><author><name sortKey="Shen, Jj" uniqKey="Shen J">JJ Shen</name></author><author><name sortKey="Xie, Y" uniqKey="Xie Y">Y Xie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miyata, Y" uniqKey="Miyata Y">Y Miyata</name></author><author><name sortKey="Sagara, Y" uniqKey="Sagara Y">Y Sagara</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S Watanabe</name></author><author><name sortKey="Asai, A" uniqKey="Asai A">A Asai</name></author><author><name sortKey="Matsuo, T" uniqKey="Matsuo T">T Matsuo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dallas, Na" uniqKey="Dallas N">NA Dallas</name></author><author><name sortKey="Samuel, S" uniqKey="Samuel S">S Samuel</name></author><author><name sortKey="Xia, L" uniqKey="Xia L">L Xia</name></author><author><name sortKey="Fan, F" uniqKey="Fan F">F Fan</name></author><author><name sortKey="Gray, Mj" uniqKey="Gray M">MJ Gray</name></author><author><name sortKey="Lim, Sj" uniqKey="Lim S">SJ Lim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, C" uniqKey="Li C">C Li</name></author><author><name sortKey="Guo, B" uniqKey="Guo B">B Guo</name></author><author><name sortKey="Wilson, Pb" uniqKey="Wilson P">PB Wilson</name></author><author><name sortKey="Stewart, A" uniqKey="Stewart A">A Stewart</name></author><author><name sortKey="Byrne, G" uniqKey="Byrne G">G Byrne</name></author><author><name sortKey="Bundred, N" uniqKey="Bundred N">N Bundred</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author><author><name sortKey="Liu, D" uniqKey="Liu D">D Liu</name></author><author><name sortKey="Yang, Z" uniqKey="Yang Z">Z Yang</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L Sun</name></author><author><name sortKey="Deng, Q" uniqKey="Deng Q">Q Deng</name></author><author><name sortKey="Yang, S" uniqKey="Yang S">S Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Hong, H" uniqKey="Hong H">H Hong</name></author><author><name sortKey="Liu, G" uniqKey="Liu G">G Liu</name></author><author><name sortKey="Bryan, Rl" uniqKey="Bryan R">RL Bryan</name></author><author><name sortKey="Cai, Wb" uniqKey="Cai W">WB Cai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ria, R" uniqKey="Ria R">R Ria</name></author><author><name sortKey="Reale, A" uniqKey="Reale A">A Reale</name></author><author><name sortKey="Castrovilli, A" uniqKey="Castrovilli A">A Castrovilli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flaten, Ge" uniqKey="Flaten G">GE Flaten</name></author><author><name sortKey="Chang, Tt" uniqKey="Chang T">TT Chang</name></author><author><name sortKey="Phillips, Wt" uniqKey="Phillips W">WT Phillips</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lim, Sk" uniqKey="Lim S">SK Lim</name></author><author><name sortKey="Shin, Dh" uniqKey="Shin D">DH Shin</name></author><author><name sortKey="Choi, Mh" uniqKey="Choi M">MH Choi</name></author><author><name sortKey="Kim, Js" uniqKey="Kim J">JS Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, Km" uniqKey="Choi K">KM Choi</name></author><author><name sortKey="Kwon, Ic" uniqKey="Kwon I">IC Kwon</name></author><author><name sortKey="Ahn, Hj" uniqKey="Ahn H">HJ Ahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alexander, Cm" uniqKey="Alexander C">CM Alexander</name></author><author><name sortKey="Dabrowiak, Jc" uniqKey="Dabrowiak J">JC Dabrowiak</name></author><author><name sortKey="Maye, Mm" uniqKey="Maye M">MM Maye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morita, Y" uniqKey="Morita Y">Y Morita</name></author><author><name sortKey="Leslie, M" uniqKey="Leslie M">M Leslie</name></author><author><name sortKey="Kameyama, H" uniqKey="Kameyama H">H Kameyama</name></author><author><name sortKey="Volk, De" uniqKey="Volk D">DE Volk</name></author><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T Tanaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ziffels, B" uniqKey="Ziffels B">B Ziffels</name></author><author><name sortKey="Grotsch, A" uniqKey="Grotsch A">A Grötsch</name></author><author><name sortKey="Al Bayati, L" uniqKey="Al Bayati L">L Al-Bayati</name></author><author><name sortKey="Neri, D" uniqKey="Neri D">D Neri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lv, Tt" uniqKey="Lv T">TT Lv</name></author><author><name sortKey="Li, Zy" uniqKey="Li Z">ZY Li</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L Xu</name></author><author><name sortKey="Zhang, Yy" uniqKey="Zhang Y">YY Zhang</name></author><author><name sortKey="Chen, Hj" uniqKey="Chen H">HJ Chen</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Hong, H" uniqKey="Hong H">H Hong</name></author><author><name sortKey="Cai, W" uniqKey="Cai W">W Cai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reinemann, C" uniqKey="Reinemann C">C Reinemann</name></author><author><name sortKey="Strehlitz, B" uniqKey="Strehlitz B">B Strehlitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ongaro, T" uniqKey="Ongaro T">T Ongaro</name></author><author><name sortKey="Matasci, M" uniqKey="Matasci M">M Matasci</name></author><author><name sortKey="Cazzamalli, S" uniqKey="Cazzamalli S">S Cazzamalli</name></author><author><name sortKey="Gouyou, B" uniqKey="Gouyou B">B Gouyou</name></author><author><name sortKey="De Luca, R" uniqKey="De Luca R">R De Luca</name></author><author><name sortKey="Neri, D" uniqKey="Neri D">D Neri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mortara, L" uniqKey="Mortara L">L Mortara</name></author><author><name sortKey="Balza, E" uniqKey="Balza E">E Balza</name></author><author><name sortKey="Bruno, A" uniqKey="Bruno A">A Bruno</name></author><author><name sortKey="Poggi, A" uniqKey="Poggi A">A Poggi</name></author><author><name sortKey="Orecchia, P" uniqKey="Orecchia P">P Orecchia</name></author><author><name sortKey="Carnemolla, B" uniqKey="Carnemolla B">B Carnemolla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Balza, E" uniqKey="Balza E">E Balza</name></author><author><name sortKey="Carnemolla, B" uniqKey="Carnemolla B">B Carnemolla</name></author><author><name sortKey="Orecchia, P" uniqKey="Orecchia P">P Orecchia</name></author><author><name sortKey="Rubartelli, A" uniqKey="Rubartelli A">A Rubartelli</name></author><author><name sortKey="Poggi, A" uniqKey="Poggi A">A Poggi</name></author><author><name sortKey="Mortara, L" uniqKey="Mortara L">L Mortara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yin, Q" uniqKey="Yin Q">Q Yin</name></author><author><name sortKey="Tang, L" uniqKey="Tang L">L Tang</name></author><author><name sortKey="Cai, K" uniqKey="Cai K">K Cai</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X Yang</name></author><author><name sortKey="Yin, L" uniqKey="Yin L">L Yin</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pezzolo, A" uniqKey="Pezzolo A">A Pezzolo</name></author><author><name sortKey="Marimpietri, D" uniqKey="Marimpietri D">D Marimpietri</name></author><author><name sortKey="Raffaghello, L" uniqKey="Raffaghello L">L Raffaghello</name></author><author><name sortKey="Cocco, C" uniqKey="Cocco C">C Cocco</name></author><author><name sortKey="Pistorio, A" uniqKey="Pistorio A">A Pistorio</name></author><author><name sortKey="Gambini, C" uniqKey="Gambini C">C Gambini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, J" uniqKey="He J">J He</name></author><author><name sortKey="Duan, S" uniqKey="Duan S">S Duan</name></author><author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name></author><author><name sortKey="Qian, Z" uniqKey="Qian Z">Z Qian</name></author><author><name sortKey="Zhou, S" uniqKey="Zhou S">S Zhou</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramot, R" uniqKey="Ramot R">R Ramot</name></author><author><name sortKey="Kishore, Ik" uniqKey="Kishore I">IK Kishore</name></author><author><name sortKey="Wilson, Cj" uniqKey="Wilson C">CJ Wilson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maeda, H" uniqKey="Maeda H">H Maeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lane, Rs" uniqKey="Lane R">RS Lane</name></author><author><name sortKey="Haller, Fm" uniqKey="Haller F">FM Haller</name></author><author><name sortKey="Chavaroche, Aae" uniqKey="Chavaroche A">AAE Chavaroche</name></author><author><name sortKey="Almond, A" uniqKey="Almond A">A Almond</name></author><author><name sortKey="Deangelis, Pl" uniqKey="Deangelis P">PL DeAngelis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hatakeyama, H" uniqKey="Hatakeyama H">H Hatakeyama</name></author><author><name sortKey="Akita, H" uniqKey="Akita H">H Akita</name></author><author><name sortKey="Harashima, H" uniqKey="Harashima H">H Harashima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Js" uniqKey="Park J">JS Park</name></author><author><name sortKey="Park, Sy" uniqKey="Park S">SY Park</name></author><author><name sortKey="Cho, Hi" uniqKey="Cho H">HI Cho</name></author><author><name sortKey="Sohn, Hj" uniqKey="Sohn H">HJ Sohn</name></author><author><name sortKey="Kim, Tg" uniqKey="Kim T">TG Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hosoi, A" uniqKey="Hosoi A">A Hosoi</name></author><author><name sortKey="Matsushita, H" uniqKey="Matsushita H">H Matsushita</name></author><author><name sortKey="Shimizu, K" uniqKey="Shimizu K">K Shimizu</name></author><author><name sortKey="Fujii, S" uniqKey="Fujii S">S Fujii</name></author><author><name sortKey="Ueha, S" uniqKey="Ueha S">S Ueha</name></author><author><name sortKey="Abe, J" uniqKey="Abe J">J Abe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chia, Wk" uniqKey="Chia W">WK Chia</name></author><author><name sortKey="Teo, M" uniqKey="Teo M">M Teo</name></author><author><name sortKey="Wang, Ww" uniqKey="Wang W">WW Wang</name></author><author><name sortKey="Lee, B" uniqKey="Lee B">B Lee</name></author><author><name sortKey="Ang, Sf" uniqKey="Ang S">SF Ang</name></author><author><name sortKey="Tai, Wm" uniqKey="Tai W">WM Tai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seidel, Uj" uniqKey="Seidel U">UJ Seidel</name></author><author><name sortKey="Oliveira, Cc" uniqKey="Oliveira C">CC Oliveira</name></author><author><name sortKey="Lampen, Mh" uniqKey="Lampen M">MH Lampen</name></author><author><name sortKey="Hall, Tv" uniqKey="Hall T">TV Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, F" uniqKey="Luo F">F Luo</name></author><author><name sortKey="Song, X" uniqKey="Song X">X Song</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Chu, Y" uniqKey="Chu Y">Y Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagpal, Ml" uniqKey="Nagpal M">ML Nagpal</name></author><author><name sortKey="Davis, J" uniqKey="Davis J">J Davis</name></author><author><name sortKey="Lin, T" uniqKey="Lin T">T Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Lu, Xl" uniqKey="Lu X">XL Lu</name></author><author><name sortKey="Zhao, Hy" uniqKey="Zhao H">HY Zhao</name></author><author><name sortKey="Zhang, Fc" uniqKey="Zhang F">FC Zhang</name></author><author><name sortKey="Jiang, Xb" uniqKey="Jiang X">XB Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Gao, Z" uniqKey="Gao Z">Z Gao</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T Zhang</name></author><author><name sortKey="Sun, B" uniqKey="Sun B">B Sun</name></author><author><name sortKey="Mu, L" uniqKey="Mu L">L Mu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vasievich, Ea" uniqKey="Vasievich E">EA Vasievich</name></author><author><name sortKey="Ramishetti, S" uniqKey="Ramishetti S">S Ramishetti</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author><author><name sortKey="Huang, L" uniqKey="Huang L">L Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alvarez Arias, Da" uniqKey="Alvarez Arias D">DA Alvarez Arias</name></author><author><name sortKey="Kim, Hj" uniqKey="Kim H">HJ Kim</name></author><author><name sortKey="Zhou, P" uniqKey="Zhou P">P Zhou</name></author><author><name sortKey="Holderried, Ta" uniqKey="Holderried T">TA Holderried</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Dranoff, G" uniqKey="Dranoff G">G Dranoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Filipazzi, P" uniqKey="Filipazzi P">P Filipazzi</name></author><author><name sortKey="Valenti, R" uniqKey="Valenti R">R Valenti</name></author><author><name sortKey="Huber, V" uniqKey="Huber V">V Huber</name></author><author><name sortKey="Pilla, L" uniqKey="Pilla L">L Pilla</name></author><author><name sortKey="Canese, P" uniqKey="Canese P">P Canese</name></author><author><name sortKey="Iero, M" uniqKey="Iero M">M Iero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poschke, I" uniqKey="Poschke I">I Poschke</name></author><author><name sortKey="Mao, Y" uniqKey="Mao Y">Y Mao</name></author><author><name sortKey="Adamson, L" uniqKey="Adamson L">L Adamson</name></author><author><name sortKey="Salazar Onfray, F" uniqKey="Salazar Onfray F">F Salazar-Onfray</name></author><author><name sortKey="Masucci, G" uniqKey="Masucci G">G Masucci</name></author><author><name sortKey="Kiessling, R" uniqKey="Kiessling R">R Kiessling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, Jm" uniqKey="Weiss J">JM Weiss</name></author><author><name sortKey="Subleski, Jj" uniqKey="Subleski J">JJ Subleski</name></author><author><name sortKey="Back, T" uniqKey="Back T">T Back</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Watkins, Sk" uniqKey="Watkins S">SK Watkins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weide, B" uniqKey="Weide B">B Weide</name></author><author><name sortKey="Martens, A" uniqKey="Martens A">A Martens</name></author><author><name sortKey="Zelba, H" uniqKey="Zelba H">H Zelba</name></author><author><name sortKey="Stutz, C" uniqKey="Stutz C">C Stutz</name></author><author><name sortKey="Derhovanessian, E" uniqKey="Derhovanessian E">E Derhovanessian</name></author><author><name sortKey="Di Giacomo, Am" uniqKey="Di Giacomo A">AM Di Giacomo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pereira, S" uniqKey="Pereira S">S Pereira</name></author><author><name sortKey="Teixeira, L" uniqKey="Teixeira L">L Teixeira</name></author><author><name sortKey="Aguilar, E" uniqKey="Aguilar E">E Aguilar</name></author><author><name sortKey="Oliveira, M" uniqKey="Oliveira M">M Oliveira</name></author><author><name sortKey="Savassi Rocha, A" uniqKey="Savassi Rocha A">A Savassi-Rocha</name></author><author><name sortKey="Pelaez, Jn" uniqKey="Pelaez J">JN Pelaez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zou, Q" uniqKey="Zou Q">Q Zou</name></author><author><name sortKey="Wu, B" uniqKey="Wu B">B Wu</name></author><author><name sortKey="Xue, J" uniqKey="Xue J">J Xue</name></author><author><name sortKey="Fan, X" uniqKey="Fan X">X Fan</name></author><author><name sortKey="Feng, C" uniqKey="Feng C">C Feng</name></author><author><name sortKey="Geng, S" uniqKey="Geng S">S Geng</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M Wang</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Verneris, Mr" uniqKey="Verneris M">MR Verneris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hermans, C" uniqKey="Hermans C">C Hermans</name></author><author><name sortKey="Anz, D" uniqKey="Anz D">D Anz</name></author><author><name sortKey="Engel, J" uniqKey="Engel J">J Engel</name></author><author><name sortKey="Kirchner, T" uniqKey="Kirchner T">T Kirchner</name></author><author><name sortKey="Endres, S" uniqKey="Endres S">S Endres</name></author><author><name sortKey="Mayr, D" uniqKey="Mayr D">D Mayr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Zk" uniqKey="Yang Z">ZK Yang</name></author><author><name sortKey="Qi, Yx" uniqKey="Qi Y">YX Qi</name></author><author><name sortKey="Lai, N" uniqKey="Lai N">N Lai</name></author><author><name sortKey="Zhang, Jh" uniqKey="Zhang J">JH Zhang</name></author><author><name sortKey="Chen, Zh" uniqKey="Chen Z">ZH Chen</name></author><author><name sortKey="Liu, My" uniqKey="Liu M">MY Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sendo, S" uniqKey="Sendo S">S Sendo</name></author><author><name sortKey="Saegusa, J" uniqKey="Saegusa J">J Saegusa</name></author><author><name sortKey="Okano, T" uniqKey="Okano T">T Okano</name></author><author><name sortKey="Takahashi, S" uniqKey="Takahashi S">S Takahashi</name></author><author><name sortKey="Akashi, K" uniqKey="Akashi K">K Akashi</name></author><author><name sortKey="Morinobu, A" uniqKey="Morinobu A">A Morinobu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gamvrellis, A" uniqKey="Gamvrellis A">A Gamvrellis</name></author><author><name sortKey="Leong, D" uniqKey="Leong D">D Leong</name></author><author><name sortKey="Hanley, Jc" uniqKey="Hanley J">JC Hanley</name></author><author><name sortKey="Xiang, Sd" uniqKey="Xiang S">SD Xiang</name></author><author><name sortKey="Mottram, P" uniqKey="Mottram P">P Mottram</name></author><author><name sortKey="Plebanski, M" uniqKey="Plebanski M">M Plebanski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dumas, A" uniqKey="Dumas A">A Dumas</name></author><author><name sortKey="Drevo, Mal" uniqKey="Drevo M">MAL Drévo</name></author><author><name sortKey="Moreau, Mf" uniqKey="Moreau M">MF Moreau</name></author><author><name sortKey="Guillet, C" uniqKey="Guillet C">C Guillet</name></author><author><name sortKey="Basle, Mf" uniqKey="Basle M">MF Baslé</name></author><author><name sortKey="Chappard, D" uniqKey="Chappard D">D Chappard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, L" uniqKey="Wu L">L Wu</name></author><author><name sortKey="Yun, Z" uniqKey="Yun Z">Z Yun</name></author><author><name sortKey="Tagawa, T" uniqKey="Tagawa T">T Tagawa</name></author><author><name sortKey="Rey Mcintyre, K" uniqKey="Rey Mcintyre K">K Rey-McIntyre</name></author><author><name sortKey="Anraku, M" uniqKey="Anraku M">M Anraku</name></author><author><name sortKey="De Perrot, M" uniqKey="De Perrot M">M de Perrot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sevko, A" uniqKey="Sevko A">A Sevko</name></author><author><name sortKey="Michels, T" uniqKey="Michels T">T Michels</name></author><author><name sortKey="Vrohlings, M" uniqKey="Vrohlings M">M Vrohlings</name></author><author><name sortKey="Umansky, L" uniqKey="Umansky L">L Umansky</name></author><author><name sortKey="Beckhove, P" uniqKey="Beckhove P">P Beckhove</name></author><author><name sortKey="Kato, M" uniqKey="Kato M">M Kato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jia, Z" uniqKey="Jia Z">Z Jia</name></author><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Fan, L" uniqKey="Fan L">L Fan</name></author><author><name sortKey="Sheng, W" uniqKey="Sheng W">W Sheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mukhtar, Ra" uniqKey="Mukhtar R">RA Mukhtar</name></author><author><name sortKey="Moore, Ap" uniqKey="Moore A">AP Moore</name></author><author><name sortKey="Nseyo, O" uniqKey="Nseyo O">O Nseyo</name></author><author><name sortKey="Baehner, Fl" uniqKey="Baehner F">FL Baehner</name></author><author><name sortKey="Au, A" uniqKey="Au A">A Au</name></author><author><name sortKey="Moore, Dh" uniqKey="Moore D">DH Moore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kato, K" uniqKey="Kato K">K Kato</name></author><author><name sortKey="Kawashiri, S" uniqKey="Kawashiri S">S Kawashiri</name></author><author><name sortKey="Yoshizawa, K" uniqKey="Yoshizawa K">K Yoshizawa</name></author><author><name sortKey="Kitahara, H" uniqKey="Kitahara H">H Kitahara</name></author><author><name sortKey="Okamune, A" uniqKey="Okamune A">A Okamune</name></author><author><name sortKey="Sugiura, S" uniqKey="Sugiura S">S Sugiura</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Theranostics</journal-id><journal-id journal-id-type="iso-abbrev">Theranostics</journal-id><journal-id journal-id-type="publisher-id">thno</journal-id><journal-title-group><journal-title>Theranostics</journal-title></journal-title-group><issn pub-type="epub">1838-7640</issn><publisher><publisher-name>Ivyspring International Publisher</publisher-name><publisher-loc>Sydney</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31281532</article-id><article-id pub-id-type="pmc">6592167</article-id><article-id pub-id-type="doi">10.7150/thno.33383</article-id><article-id pub-id-type="publisher-id">thnov09p4066</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Xiaomei</given-names></name><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Jing</given-names></name><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Duan</surname><given-names>Siliang</given-names></name><xref ref-type="author-notes" rid="FNA_star">*</xref></contrib><contrib contrib-type="author"><name><surname>Hou</surname><given-names>Xiaoqiong</given-names></name></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Xi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Hu</surname><given-names>Zixi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tang</surname><given-names>Zhuoran</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mo</surname><given-names>Fengzhen</given-names></name></contrib><contrib contrib-type="author"><name><surname>Lu</surname><given-names>Xiaoling</given-names></name><xref ref-type="corresp" rid="FNA_envelop">✉</xref></contrib></contrib-group><aff>Nanobody Research Center/School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China</aff><author-notes><corresp id="FNA_envelop">✉ Corresponding author: Xiaoling Lu, Ph.D., Professor, Nanobody Research Center, Guangxi Medical University, Nanning, Guangxi, 530021, China. Tel: (86) 771-5317 061; Fax: (86) 771-5317 061. E-mail: <email>luxiaoling@gxmu.edu.cn</email></corresp><fn fn-type="equal" id="FNA_star"><p><sup>*</sup>These authors contributed equally to this work.</p></fn><fn fn-type="COI-statement"><p>Competing Interests: The authors have declared that no competing interest exists.</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>31</day><month>5</month><year>2019</year></pub-date><volume>9</volume><issue>14</issue><fpage>4066</fpage><lpage>4083</lpage><history><date date-type="received"><day>21</day><month>1</month><year>2019</year></date><date date-type="accepted"><day>24</day><month>3</month><year>2019</year></date></history><permissions><copyright-statement>© Ivyspring International Publisher</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc/4.0/">https://creativecommons.org/licenses/by-nc/4.0/</ext-link>). See <ext-link ext-link-type="uri" xlink:href="http://ivyspring.com/terms">http://ivyspring.com/terms</ext-link> for full terms and conditions.</license-p></license></permissions><abstract><p><bold>Background</bold>: Adequate recruitment of highly active tumor antigen-specific cytotoxic T lymphocytes (CTLs) remains a major challenge in cancer immunotherapy.</p><p><bold>Objective</bold>: To construct liposome (LP)-based nanocapsules with surface endoglin aptamer (ENG-Apt) encapsulating mouse interferon-inducible protein-10 (mIP-10), with the ability to target mouse tumor vascular endothelial cells (mTECs) and enhance CTLs targeting and recruitment to the tumor vasculature.</p><p><bold>Methods</bold>: ENG-Apt/mIP-10-LP nanocapsules were prepared by grafting DSPE-PEG<sub>2000</sub>-ENG-Apt on the surface of liposomes containing mIP-10 plasmids, characterized and assessed for the cell binding specificity<italic> in vitro</italic>. The tumor-targeting ability of ENG-Apt/mIP-10-LP nanocapsules was evaluated<italic> in vivo</italic>. The anti-tumor efficacy of ENG-Apt/mIP-10-LP nanocapsules treatment, as well as the combination treatment of ENG-Apt/mIP-10-LP nanocapsules and adoptive TRP2CD8<sup>+</sup> T cells, were both tested in melanoma-bearing mice, by evaluation of the tumor volume and the mouse survival time. To discuss the anti-tumoral mechanism of ENG-Apt/mIP-10-LP nanocapsules-based therapies, IFN-γ secretion, proportion of TRP2CD8<sup>+</sup> T cells among TILs, MDSCs in the tumor microenvironment and Tregs in the spleen, were determined after the treatments. Proliferation and apoptosis of tumor cells, and tumor angiogenesis were also assessed.</p><p><bold>Results</bold>: The prepared ENG-Apt/mIP-10-LP nanocapsules possess an adequate nanometric size, good stability, high specificity to mTECs and tumor sites, along with the ability to induce mIP-10 expression <italic>in vitro</italic> and<italic> in vivo</italic>. Treatment of ENG-Apt/mIP-10-LP nanocapsules demonstrated CTLs enrichment into the tumor site, which inhibited tumor cell proliferation and angiogenesis, as well as promoted tumor-cell apoptosis, leading to a decrease in tumor progression and prolonged survival time in melanoma tumor-bearing mice. In addition, the proportion of MDSCs and Tregs was found to decrease. The combination of ENG-Apt/mIP-10-LP nanocapsules with adoptive TRP2CD8<sup>+</sup> T cells, showed stronger abilities in inhibiting tumor growth and increasing animal survival time, thereby displayed an enhanced anti-melanoma tumor efficacy, due to the recruitment of both endogenous CD8<sup>+</sup> T cells and exogenous TRP2CD8<sup>+</sup> T cells <italic>in vivo</italic>.</p><p><bold>Conclusion</bold>: ENG-Apt/mIP-10-LP nanocapsules could enhance the recruitment of both endogenous and exogenous CTLs specifically targeting melanoma tumor vasculatures and exert anti-tumoral effect, therefore provides a potentially novel strategy for tumor immunotherapy.</p></abstract><kwd-group><kwd>Endoglin aptamer</kwd><kwd>IP-10</kwd><kwd>nanocarriers</kwd><kwd>tumor vasculatures</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" position="float"><label>Figure 1</label><caption><p>Characterization of ENG-Apt/mIP-10-LP nanocapsules: Representative TEM images and size distributions of <bold>(A)</bold> LPs and <bold>(B)</bold> ENG-Apt/mIP-10-LP nanocapsules. Scale bar on TEM images is 200 nm (upper) and 100 nm (blow). N/P ratio of LPs and ENG-Apt/mIP-10-LP nanocapsules is 1:1.<bold>(C)</bold> shows the particle sizes and zeta potentials of different types of nanoparticles and ENG-Apt/mIP-10-LP nanocapsules prepared with different ratios of N/P. <bold>(D)</bold> Detection of mIP-10 expression after treatment with mIP-10-LPs or ENG-Apt/mIP-10-LP nanocapsules in 1% agarose gel electrophoresis (Lane 1: mIP-10, Lane 2: mIP-10-LPs, Lane 3: ENG-Apt/mIP-10-LP, Lane 4: mIP-10-LPs + Triton X-100, Lane 5: ENG-Apt/mIP-10-LP + Triton X-100, Lane 6: LP + Triton X-100, Lane 7: mIP-10 + Triton X-100). <bold>(E)</bold> Identification of ENG-Apt binding to LP in 3% gel retardation assay analysis of ENG-Aptamer binding to LP surface (Lane 1: ENG-Aptamer, Lane 2: LP, Lane 3: LP + ENG-Aptamer, Lane 4: unpurified ENG-Apt-LP, Lane 5: purified ENG-Apt-LP).</p></caption><graphic xlink:href="thnov09p4066g001"></graphic></fig><fig id="F2" position="float"><label>Figure 2</label><caption><p>ENG-Apt/mIP-10-LP nanocapsules target mTECs to increase mTEC expression of mIP-10.<bold> (A, B)</bold> ENG-Apt/mIP-10-LP nanocapsules specifically bind to mTECs through ENG receptors as is evident by the fluorescence of DiI-labeled liposomes (red), DAPI-stained nuclei (blue), and FITC-labeled ENG-Apt (green), at a magnification of 400×. <bold>(C)</bold> the fluorescence intensity in mTECs after binding of ENG-Apt/mIP-10-LP nanocapsules is 16 times greater than that with mIP-10-LPs. <bold>(D)</bold> the fluorescence intensity analysis in mTECs and B16 after binding of ENG-Apt/mIP-10-LP nanocapsules. <bold>(E)</bold> Fluorescence intensity analysis showing ENG-Apt/mIP-10-LP nanocapsules has high binding rate with mTECs. <bold>(F)</bold> Flow cytometric analysis showing ENG-Apt/mIP-10-LP nanocapsules has high binding rate with mTECs rather than the controls. Mean ± SE of three independent experiments is shown. <italic>** p < 0.01.</italic></p></caption><graphic xlink:href="thnov09p4066g002"></graphic></fig><fig id="F3" position="float"><label>Figure 3</label><caption><p>ENG-Apt/mIP-10-LP nanocapsules targeted to tumor tissues result in high expression of IP-10 protein. B16 cells (5×10<sup>5</sup> cells/mouse) were implanted via subcutaneous injection in the left armpit of 4-week-old female inbred BALB/c athymic nude mice. Once the tumors reached a volume of 500 mm<sup>3</sup>, tumor-bearing mice received one of three treatments via intravenous tail injections: 0.6 mg DilC<sub>18</sub>(7) (DiR)/kg body weight (DiR control), DiR-labeled mIP-10-LPs, and ENG-Apt/mIP-10-LP nanocapsules. The distribution of the fluorescent particles in each group was detected using an <italic>in vivo</italic> imaging system (In Vivo FX PRO, Bruker, Billerica, MA, USA) (excitation at 720 nm, emission at 790 nm) at 2, 6, 24, 48 and 72 hours after injection. <bold>(A)</bold><italic> In vivo</italic> distribution of DiR-labeled nanocapsules in tumor-bearing mice. <bold>(B)</bold> Relative fluorescent intensity (RFI) of nanocapsules in tumor tissues, RFI in tumor tissues 48 h after delivery of DiR-labeled ENG-Apt/mIP-10-LPs is 2.5 times more than that achieved with mIP-10-LPs. <bold>(C)</bold> The expression of mIP-10 protein in tumor tissues of various groups detection by immunohistochemical staining (magnification, 400×). <bold>(D)</bold> Statistical quantification of mIP-10 protein expression in tumor tissues of various groups. The mean ± SE of three independent experiments is shown. ** <italic>p < 0.01</italic> for the comparison of the ENG-Apt/mIP-10-LP group to control groups.</p></caption><graphic xlink:href="thnov09p4066g003"></graphic></fig><fig id="F4" position="float"><label>Figure 4</label><caption><p>Tumor volume and survival time in melanoma-bearing mice in different treatment groups. <bold>(A, B, C)</bold> Anti-tumor effect of the treatment with ENG-Apt/mIP-10-LP nanocapsules in melanoma-bearing mice. (A) Experiment design for the treatment of melanoma-bearing mice with ENG-Apt/mIP-10-LP nanocapsules. B16 cells (5×10<sup>5</sup> cells/mouse) were inoculated into the right groin area of the C57BL/6 mice via subcutaneous injection. On the fifth day after the tumor cell inoculation, these tumor-bearing mice were then randomized into four groups (n=5), and respectively treated with PBS, mIP-10 plasmid, mIP-10-LPs, or ENG-Apt/mIP-10-LP nanocapsules at 5, 8, 11, and 14 days after tumor cells inoculation via tail vein intravenous injections. Another 32 mice subjected to the same treatments (n=8) were monitored to generate survival curves. <bold>(B)</bold> Showing tumor growth curves in mm<sup>3</sup> among groups over the days after the treatment (n=5). <bold>(C)</bold> showing the survival rates of mice among groups over the days after the treatment (n=8). * <italic>p < 0.05,</italic> ** <italic>p <0.01</italic> for the comparison of survival percentage in the ENG-Apt/mIP-10-LP group and control groups. <bold>(D, E, F)</bold> Anti-tumor effect of combination treatment with ENG-Apt/mIP-10-LP nanocapsules and adoptive TRP2CD8<sup>+</sup> T cells in melanoma-bearing mice. (D) Experiment design for the combination treatment of melanoma-bearing mice with ENG-Apt/mIP-10-LP and TRP2-specific CD8<sup>+</sup> T cells. C57BL/6 mice were randomized into five groups (n=5). Four days after subcutaneous inoculation of B16 cells, CD8<sup>+</sup> T cells or TRP2-specific CD8<sup>+</sup> T cells were resuspended in PBS at 1.5×10<sup>7</sup> cells/mL (200 µL/mouse) via the tailvein injection<italic> in vivo</italic>. The next day, PBS and ENG-Apt/mIP-10-LP nanocapsules (mIP-10 plasmid, 50 µg/mouse) were also injected intravenously in the corresponding groups. Mice of different groups were treated at 5, 8, 11, and 14 days after tumor cells inoculation via tail vein intravenous injections. Another 40 mice subjected to the same treatments (n=8) were monitored to generate survival curves. (E) showing tumor growth curves in mm<sup>3</sup> among groups over the days after the treatment (n=5). (F) showing the survival rates of mice among groups over the days after the treatment. * <italic>p < 0.05,</italic> ** <italic>p < 0.01</italic> for the comparison of survival percentage between the ENG-Apt/mIP-10-LP + TRP2CD8<sup>+</sup> T group and control groups. Mean ± SE of three independent experiments is shown.</p></caption><graphic xlink:href="thnov09p4066g004"></graphic></fig><fig id="F5" position="float"><label>Figure 5</label><caption><p>Combination of ENG-Apt/mIP-10-LP nanocapsules and TRP2CD8<sup>+</sup> T cells increase the number and activity of tumor cell-specific CD8<sup>+</sup> T cells in tumor tissues. <bold>(A)</bold> Frequencies of TRP2CD8<sup>+</sup> T cells in tumor tissues of various groups detected by flow cytometry.<bold> (B)</bold> TRP2CD8<sup>+</sup> T cells infiltration in tumor tissues of various groups detected by ISTS. Fluorescence images of tissue sections stained with CD8<sup>+</sup> T in green, TRP2 tetramer in red and cell nuclei were labeled with DAPI (blue).<bold> (C)</bold> TRP2-specific IFN-γ-secreting cells among TILs detected by immunospot staining.<bold> (D)</bold> Requencies of TRP2CD8<sup>+</sup> T cells among TILs.<bold> (E)</bold> Frequencies of CD8<sup>+</sup> T cells among TILs.<bold> (F)</bold> The numbers of TRP2-specific IFN-γ-positive cells among TILs. The mean ± SE of three independent experiments is shown. ** <italic>p</italic> < 0.01 for the comparison of the ENG-Apt/mIP-10-LP + TRP2CD8<sup>+</sup> T cell group to control groups. Mean ± SE of three independent experiments is shown.</p></caption><graphic xlink:href="thnov09p4066g005"></graphic></fig><fig id="F6" position="float"><label>Figure 6</label><caption><p>Combination treatment with ENG-Apt/mIP-10-LP and TRP2CD8<sup>+</sup> T cells reduced the amounts of MDSCs and Tregs in the tumor microenvironment. The flow cytometric analyses for MDSC and Treg showed that the percentage of CD11b<sup>+</sup>Gr1<sup>+</sup> MDSC in single cells of tumor tissue of mice treated with ENG-Apt/mIp-10-LP combined with TRP2CD8<sup>+</sup> T cells was significantly reduced and significantly lower than that of other control groups. The percentage of CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs in TIL was also significantly reduced. <bold>(A)</bold> The percentages of MDSCs in tumor tissues detected by flow cytometry. <bold>(B)</bold> The percentages of Tregs in tumor tissues; results with CD4<sup>+</sup> gating are shown. <bold>(C)</bold> The quantified numbers of MDSCs in tumor tissues. <bold>(D)</bold> The quantified numbers of Tregs in tumor tissues. The mean ± SE of three independent experiments is shown. ** <italic>p</italic> < 0.01 for the comparison of ENG-Apt/mIP-10-LP + TRP2CD8<sup>+</sup> T cell group to control groups.</p></caption><graphic xlink:href="thnov09p4066g006"></graphic></fig><fig id="F7" position="float"><label>Figure 7</label><caption><p>Combination treatment with ENG-Apt/mIP-10-LP and TRP2CD8<sup>+</sup> T cells inhibits tumor cell proliferation, promotes tumor cell apoptosis, and suppresses tumor angiogenesis. <bold>(A)</bold> Detection for Proliferating cell nuclear antigen expression (PCNA) by IHC staining, at a magnification of 400×. <bold>(B)</bold> Results of tumor apoptosis detection by TUNEL assay; nuclei stained blue, positive cells stained green, at 200×. <bold>(B)</bold> Tumor microvascular densities detected by CD105 monoclonal antibodies, at 100×. <bold>(D)</bold> Statistical quantification of PCNA numbers in various groups. <bold>(E)</bold> Statistical quantification of tumor apoptosis numbers in various groups. <bold>(F)</bold> Statistical quantification of tumor microvasculature number in various groups. The mean ± SE of three independent experiments is shown. * <italic>p</italic> < 0.05 and ** <italic>p</italic> < 0.01 for comparison of ENG-Apt/mIP-10-LP + TRP2CD8<sup>+</sup> T cells group to other controls.</p></caption><graphic xlink:href="thnov09p4066g007"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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