Intracellular Trafficking Network and Autophagy of PHBHHx Nanoparticles and their Implications for Drug Delivery
Identifieur interne : 000713 ( Main/Exploration ); précédent : 000712; suivant : 000714Intracellular Trafficking Network and Autophagy of PHBHHx Nanoparticles and their Implications for Drug Delivery
Auteurs : Xiangyu Sun [République populaire de Chine] ; Cheng Cheng [République populaire de Chine] ; Jinxie Zhang [République populaire de Chine] ; Xing Jin [République populaire de Chine] ; Shuqing Sun [République populaire de Chine] ; Lin Mei [République populaire de Chine] ; Laiqiang Huang [République populaire de Chine]Source :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx), which is naturally generated by biodegradable polyhydroxyalkanoates synthesized by bacteria, is an attractive material for drug delivery due to its controllable physical properties, non-toxicity, environmental friendliness, degradable properties and good biocompatibility. However, the intracellular trafficking network pathways, especially the autophagy mechanism of PHBHHx nanoparticles (NPs), have rarely been investigated. In this paper, we successfully prepared the NPs used solvent displacement method and investigated the autophagy pathways and other intracellular trafficking mechanisms based on NPs with the assistance of Rab proteins. We found that NPs were internalized in cells mainly via clathrin endocytosis and caveolin endocytosis. Beside the classical pathways, we discovered two new pathways: the micropinocytosis early endosome (EEs)-micropinocytosis-lysosome pathway and the EEs-liposome-lysosome pathway. NPs were delivered to cells through endocytosis recycling vesicles and GLUT4 exocytosis vesicles. Similar to other nanoparticles, NPs also induced intracellular autophagy and were then degraded via endolysosomal pathways. 3-MA and CQ were used as autophagy inhibitors to avoid the degradation of NPs through lysosomes by blocking endolysosomal pathways. Tumor volumes and weights were significantly decreased when autophagy inhibitors and chemical drugs packaged in NPs were cooperatively used.
Url:
DOI: 10.1038/s41598-019-45632-y
PubMed: 31270337
PubMed Central: 6610140
Affiliations:
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institution-id-type="GRID">grid.12527.33</institution-id><institution>School of Life Sciences,</institution><institution>Tsinghua University,</institution></institution-wrap>Beijing, 100084 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</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 id="Par1">3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx), which is naturally generated by biodegradable polyhydroxyalkanoates synthesized by bacteria, is an attractive material for drug delivery due to its controllable physical properties, non-toxicity, environmental friendliness, degradable properties and good biocompatibility. However, the intracellular trafficking network pathways, especially the autophagy mechanism of PHBHHx nanoparticles (NPs), have rarely been investigated. In this paper, we successfully prepared the NPs used solvent displacement method and investigated the autophagy pathways and other intracellular trafficking mechanisms based on NPs with the assistance of Rab proteins. We found that NPs were internalized in cells mainly via clathrin endocytosis and caveolin endocytosis. Beside the classical pathways, we discovered two new pathways: the micropinocytosis early endosome (EEs)-micropinocytosis-lysosome pathway and the EEs-liposome-lysosome pathway. NPs were delivered to cells through endocytosis recycling vesicles and GLUT4 exocytosis vesicles. Similar to other nanoparticles, NPs also induced intracellular autophagy and were then degraded via endolysosomal pathways. 3-MA and CQ were used as autophagy inhibitors to avoid the degradation of NPs through lysosomes by blocking endolysosomal pathways. Tumor volumes and weights were significantly decreased when autophagy inhibitors and chemical drugs packaged in NPs were cooperatively used.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hao, J" uniqKey="Hao J">J Hao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Xd" uniqKey="Wang X">XD Wang</name></author><author><name sortKey="Gu, Xq" uniqKey="Gu X">XQ Gu</name></author><author><name sortKey="Wang, Hm" uniqKey="Wang H">HM Wang</name></author><author><name sortKey="Yang, Jy" uniqKey="Yang J">JY Yang</name></author><author><name sortKey="Mao, Sr" uniqKey="Mao S">SR Mao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, Xl" uniqKey="Guo X">XL 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Ramona Neunuebel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akinc, A" uniqKey="Akinc A">A Akinc</name></author><author><name sortKey="Battaglia, G" uniqKey="Battaglia G">G Battaglia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bruinsma, S" uniqKey="Bruinsma S">S Bruinsma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N Mizushima</name></author><author><name sortKey="Komatsu, M" uniqKey="Komatsu M">M Komatsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mei, L" uniqKey="Mei L">L Mei</name></author><author><name sortKey="Zhang, Xd" uniqKey="Zhang X">XD Zhang</name></author><author><name sortKey="Feng, Ss" uniqKey="Feng S">SS Feng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szatmari, Z" uniqKey="Szatmari Z">Z Szatmári</name></author><author><name sortKey="Sass, M" uniqKey="Sass M">M Sass</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levine, B" uniqKey="Levine B">B Levine</name></author><author><name sortKey="Kroemer, G" uniqKey="Kroemer G">G Kroemer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penaloza, Jp" uniqKey="Penaloza J">JP Penaloza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeng, Xw" uniqKey="Zeng X">XW Zeng</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hoyer Hansen, M" uniqKey="Hoyer Hansen M">M Hoyer-Hansen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liang, X" uniqKey="Liang X">X Liang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Sun, Xiangyu" sort="Sun, Xiangyu" uniqKey="Sun X" first="Xiangyu" last="Sun">Xiangyu Sun</name></noRegion><name sortKey="Cheng, Cheng" sort="Cheng, Cheng" uniqKey="Cheng C" first="Cheng" last="Cheng">Cheng Cheng</name><name sortKey="Huang, Laiqiang" sort="Huang, Laiqiang" uniqKey="Huang L" first="Laiqiang" last="Huang">Laiqiang Huang</name><name sortKey="Huang, Laiqiang" sort="Huang, Laiqiang" uniqKey="Huang L" first="Laiqiang" last="Huang">Laiqiang Huang</name><name sortKey="Jin, Xing" sort="Jin, Xing" uniqKey="Jin X" first="Xing" last="Jin">Xing Jin</name><name sortKey="Mei, Lin" sort="Mei, Lin" uniqKey="Mei L" first="Lin" last="Mei">Lin Mei</name><name sortKey="Sun, Shuqing" sort="Sun, Shuqing" uniqKey="Sun S" first="Shuqing" last="Sun">Shuqing Sun</name><name sortKey="Sun, Shuqing" sort="Sun, Shuqing" uniqKey="Sun S" first="Shuqing" last="Sun">Shuqing Sun</name><name sortKey="Sun, Xiangyu" sort="Sun, Xiangyu" uniqKey="Sun X" first="Xiangyu" last="Sun">Xiangyu Sun</name><name sortKey="Zhang, Jinxie" sort="Zhang, Jinxie" uniqKey="Zhang J" first="Jinxie" last="Zhang">Jinxie Zhang</name><name sortKey="Zhang, Jinxie" sort="Zhang, Jinxie" uniqKey="Zhang J" first="Jinxie" last="Zhang">Jinxie Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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