Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy.
Identifieur interne : 000064 ( Main/Exploration ); précédent : 000063; suivant : 000065Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy.
Auteurs : Man Li [République populaire de Chine] ; Mengmeng Li [République populaire de Chine] ; Yiliang Yang [République populaire de Chine] ; Yingke Liu [République populaire de Chine] ; Hanbing Xie [République populaire de Chine] ; Qianwen Yu [République populaire de Chine] ; Lifeng Tian [République populaire de Chine] ; Xian Tang [République populaire de Chine] ; Kebai Ren [République populaire de Chine] ; Jianping Li [République populaire de Chine] ; Zhirong Zhang [République populaire de Chine] ; Qin He [République populaire de Chine]Source :
- Journal of controlled release : official journal of the Controlled Release Society [ 1873-4995 ] ; 2020.
Abstract
Immunotherapy has exhibited great potential in cancer treatment. However, for immunosuppressive tumors such as pancreatic cancer, immunotherapy is far from satisfactory. PI3K-γ and colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) pathways are involved in the infiltration and polarization of immunosuppressive cells including M2 tumor associated macrophages (M2 TAMs), causing a suppressive tumor immune microenvironment (TIME) in pancreatic cancer. Herein, a M2 TAM targeting nanomicelle was developed to co-deliver PI3K-γ inhibitor NVP-BEZ 235 and CSF-1R-siRNA for specific TAMs reprogramming and antitumor immune responses activation. M2 TAM targeting peptide M2pep was modified on a mixed micelle, which was potent to co-encapsulate BEZ 235 and CSF-1R siRNA. The formulated nanomicelle increased M2 TAM targeting efficiency both in vitro and in vivo. Compared with single pathway blockade, dual blockade of PI3k-γ and CSF-1R demonstrated enhanced TAM remodeling effects by reducing M2 TAM level and elevating M1 TAM level, and also suppressed tumor infiltration of myeloid-derived suppressor cells (MDSCs). Consequently, the M2 TAM targeting reprogramming system activated antitumor immune responses and achieved enhanced anti-pancreatic tumor effects via PI3K-γ blockade and downregulation of CSF-1R. The M2pep modified nanomicelle provides a promising method for co-delivery of siRNA and small molecule inhibitor to M2 TAM. Dual inhibition of both PI3K-γ and CSF-1R can remodel TIME and activate antitumor immune responses synergistically, providing an alternative approach for pancreatic cancer treatment.
DOI: 10.1016/j.jconrel.2020.02.011
PubMed: 32035193
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy.</title><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Li, Mengmeng" sort="Li, Mengmeng" uniqKey="Li M" first="Mengmeng" last="Li">Mengmeng Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Yiliang" sort="Yang, Yiliang" uniqKey="Yang Y" first="Yiliang" last="Yang">Yiliang Yang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Yingke" sort="Liu, Yingke" uniqKey="Liu Y" first="Yingke" last="Liu">Yingke Liu</name><affiliation wicri:level="1"><nlm:affiliation>West China School of Stomotology, Sichuan University, Chengdu, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>West China School of Stomotology, Sichuan University, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Hanbing" sort="Xie, Hanbing" uniqKey="Xie H" first="Hanbing" last="Xie">Hanbing Xie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, The Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, The Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Qianwen" sort="Yu, Qianwen" uniqKey="Yu Q" first="Qianwen" last="Yu">Qianwen Yu</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Tian, Lifeng" sort="Tian, Lifeng" uniqKey="Tian L" first="Lifeng" last="Tian">Lifeng Tian</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Xian" sort="Tang, Xian" uniqKey="Tang X" first="Xian" last="Tang">Xian Tang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Ren, Kebai" sort="Ren, Kebai" uniqKey="Ren K" first="Kebai" last="Ren">Kebai Ren</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Li, Jianping" sort="Li, Jianping" uniqKey="Li J" first="Jianping" last="Li">Jianping Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Zhirong" sort="Zhang, Zhirong" uniqKey="Zhang Z" first="Zhirong" last="Zhang">Zhirong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="He, Qin" sort="He, Qin" uniqKey="He Q" first="Qin" last="He">Qin He</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address: qinhe@scu.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32035193</idno><idno type="pmid">32035193</idno><idno type="doi">10.1016/j.jconrel.2020.02.011</idno><idno type="wicri:Area/Main/Corpus">000219</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000219</idno><idno type="wicri:Area/Main/Curation">000219</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000219</idno><idno type="wicri:Area/Main/Exploration">000219</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy.</title><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Li, Mengmeng" sort="Li, Mengmeng" uniqKey="Li M" first="Mengmeng" last="Li">Mengmeng Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Yiliang" sort="Yang, Yiliang" uniqKey="Yang Y" first="Yiliang" last="Yang">Yiliang Yang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Yingke" sort="Liu, Yingke" uniqKey="Liu Y" first="Yingke" last="Liu">Yingke Liu</name><affiliation wicri:level="1"><nlm:affiliation>West China School of Stomotology, Sichuan University, Chengdu, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>West China School of Stomotology, Sichuan University, Chengdu</wicri:regionArea><wicri:noRegion>Chengdu</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Hanbing" sort="Xie, Hanbing" uniqKey="Xie H" first="Hanbing" last="Xie">Hanbing Xie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, The Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, The Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Qianwen" sort="Yu, Qianwen" uniqKey="Yu Q" first="Qianwen" last="Yu">Qianwen Yu</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Tian, Lifeng" sort="Tian, Lifeng" uniqKey="Tian L" first="Lifeng" last="Tian">Lifeng Tian</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Xian" sort="Tang, Xian" uniqKey="Tang X" first="Xian" last="Tang">Xian Tang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Ren, Kebai" sort="Ren, Kebai" uniqKey="Ren K" first="Kebai" last="Ren">Kebai Ren</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Li, Jianping" sort="Li, Jianping" uniqKey="Li J" first="Jianping" last="Li">Jianping Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Zhirong" sort="Zhang, Zhirong" uniqKey="Zhang Z" first="Zhirong" last="Zhang">Zhirong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author><author><name sortKey="He, Qin" sort="He, Qin" uniqKey="He Q" first="Qin" last="He">Qin He</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address: qinhe@scu.edu.cn.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064</wicri:regionArea><wicri:noRegion>Chengdu 610064</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of controlled release : official journal of the Controlled Release Society</title><idno type="eISSN">1873-4995</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Immunotherapy has exhibited great potential in cancer treatment. However, for immunosuppressive tumors such as pancreatic cancer, immunotherapy is far from satisfactory. PI3K-γ and colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) pathways are involved in the infiltration and polarization of immunosuppressive cells including M2 tumor associated macrophages (M2 TAMs), causing a suppressive tumor immune microenvironment (TIME) in pancreatic cancer. Herein, a M2 TAM targeting nanomicelle was developed to co-deliver PI3K-γ inhibitor NVP-BEZ 235 and CSF-1R-siRNA for specific TAMs reprogramming and antitumor immune responses activation. M2 TAM targeting peptide M2pep was modified on a mixed micelle, which was potent to co-encapsulate BEZ 235 and CSF-1R siRNA. The formulated nanomicelle increased M2 TAM targeting efficiency both in vitro and in vivo. Compared with single pathway blockade, dual blockade of PI3k-γ and CSF-1R demonstrated enhanced TAM remodeling effects by reducing M2 TAM level and elevating M1 TAM level, and also suppressed tumor infiltration of myeloid-derived suppressor cells (MDSCs). Consequently, the M2 TAM targeting reprogramming system activated antitumor immune responses and achieved enhanced anti-pancreatic tumor effects via PI3K-γ blockade and downregulation of CSF-1R. The M2pep modified nanomicelle provides a promising method for co-delivery of siRNA and small molecule inhibitor to M2 TAM. Dual inhibition of both PI3K-γ and CSF-1R can remodel TIME and activate antitumor immune responses synergistically, providing an alternative approach for pancreatic cancer treatment.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32035193</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>06</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-4995</ISSN><JournalIssue CitedMedium="Internet"><Volume>321</Volume><PubDate><Year>2020</Year><Month>05</Month><Day>10</Day></PubDate></JournalIssue><Title>Journal of controlled release : official journal of the Controlled Release Society</Title><ISOAbbreviation>J Control Release</ISOAbbreviation></Journal><ArticleTitle>Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy.</ArticleTitle><Pagination><MedlinePgn>23-35</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0168-3659(20)30087-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jconrel.2020.02.011</ELocationID><Abstract><AbstractText>Immunotherapy has exhibited great potential in cancer treatment. However, for immunosuppressive tumors such as pancreatic cancer, immunotherapy is far from satisfactory. PI3K-γ and colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-1R) pathways are involved in the infiltration and polarization of immunosuppressive cells including M2 tumor associated macrophages (M2 TAMs), causing a suppressive tumor immune microenvironment (TIME) in pancreatic cancer. Herein, a M2 TAM targeting nanomicelle was developed to co-deliver PI3K-γ inhibitor NVP-BEZ 235 and CSF-1R-siRNA for specific TAMs reprogramming and antitumor immune responses activation. M2 TAM targeting peptide M2pep was modified on a mixed micelle, which was potent to co-encapsulate BEZ 235 and CSF-1R siRNA. The formulated nanomicelle increased M2 TAM targeting efficiency both in vitro and in vivo. Compared with single pathway blockade, dual blockade of PI3k-γ and CSF-1R demonstrated enhanced TAM remodeling effects by reducing M2 TAM level and elevating M1 TAM level, and also suppressed tumor infiltration of myeloid-derived suppressor cells (MDSCs). Consequently, the M2 TAM targeting reprogramming system activated antitumor immune responses and achieved enhanced anti-pancreatic tumor effects via PI3K-γ blockade and downregulation of CSF-1R. The M2pep modified nanomicelle provides a promising method for co-delivery of siRNA and small molecule inhibitor to M2 TAM. Dual inhibition of both PI3K-γ and CSF-1R can remodel TIME and activate antitumor immune responses synergistically, providing an alternative approach for pancreatic cancer treatment.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Man</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Mengmeng</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Yiliang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Yingke</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>West China School of Stomotology, Sichuan University, Chengdu, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Hanbing</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, The Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Qianwen</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tian</LastName><ForeName>Lifeng</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Xian</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Kebai</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jianping</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Zhirong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He</LastName><ForeName>Qin</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address: qinhe@scu.edu.cn.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Control Release</MedlineTA><NlmUniqueID>8607908</NlmUniqueID><ISSNLinking>0168-3659</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">CSF-1R</Keyword><Keyword MajorTopicYN="Y">Immunotherapy</Keyword><Keyword MajorTopicYN="Y">M2 TAM</Keyword><Keyword MajorTopicYN="Y">PI3k-γ</Keyword><Keyword MajorTopicYN="Y">Pancreatic cancer</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>11</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>01</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>02</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32035193</ArticleId><ArticleId IdType="pii">S0168-3659(20)30087-0</ArticleId><ArticleId IdType="doi">10.1016/j.jconrel.2020.02.011</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name></noRegion><name sortKey="He, Qin" sort="He, Qin" uniqKey="He Q" first="Qin" last="He">Qin He</name><name sortKey="Li, Jianping" sort="Li, Jianping" uniqKey="Li J" first="Jianping" last="Li">Jianping Li</name><name sortKey="Li, Mengmeng" sort="Li, Mengmeng" uniqKey="Li M" first="Mengmeng" last="Li">Mengmeng Li</name><name sortKey="Liu, Yingke" sort="Liu, Yingke" uniqKey="Liu Y" first="Yingke" last="Liu">Yingke Liu</name><name sortKey="Ren, Kebai" sort="Ren, Kebai" uniqKey="Ren K" first="Kebai" last="Ren">Kebai Ren</name><name sortKey="Tang, Xian" sort="Tang, Xian" uniqKey="Tang X" first="Xian" last="Tang">Xian Tang</name><name sortKey="Tian, Lifeng" sort="Tian, Lifeng" uniqKey="Tian L" first="Lifeng" last="Tian">Lifeng Tian</name><name sortKey="Xie, Hanbing" sort="Xie, Hanbing" uniqKey="Xie H" first="Hanbing" last="Xie">Hanbing Xie</name><name sortKey="Yang, Yiliang" sort="Yang, Yiliang" uniqKey="Yang Y" first="Yiliang" last="Yang">Yiliang Yang</name><name sortKey="Yu, Qianwen" sort="Yu, Qianwen" uniqKey="Yu Q" first="Qianwen" last="Yu">Qianwen Yu</name><name sortKey="Zhang, Zhirong" sort="Zhang, Zhirong" uniqKey="Zhang Z" first="Zhirong" last="Zhang">Zhirong Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Bois/explor/PlantImRecepV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000064 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000064 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Bois
|area= PlantImRecepV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:32035193
|texte= Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32035193" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a PlantImRecepV1
| This area was generated with Dilib version V0.6.38. |  |