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A preliminary study on the interaction between Asn-Gly-Arg(NGR)-modified multifunctional nanoparticles and vascular epithelial cells

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Acta Pharmaceutica Sinica B 2017年第3期7卷 361-372页

作者： Chunxi Liu Tingxian Liu Xiaoyue Yu Yizhu Gu Department of Pharmacy Qilu HospitalShandong UniversityJi’nan 250012China School of Pharmaceutical Science Shandong UniversityJi’nan 250012China

Previously developed Asn-Gly-Arg(NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol)(PEI–PEG)-based nanoparticles(TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin(DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells(HUVEC) to better understand the cellular entry mechanism. In the present investigation,experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13(APN/CD13) and caveolin 1(CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment,TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin(MβCD), further identifying the involvement of caveolae-mediated endocytosis(CvME). This conclusion was also verified by endocytosis inhibitor experiments.

关键词： Asn-Gly-Arg peptide Aminopeptidase N/CD13 Caveolin 1 caveolae-mediated endocytosis Endothelial cells Cellular entry Co-localization Doxorubicin

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Miriplatin-loaded liposome,as a novel mitophagy inducer,suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4477-4501页

作者： Xiaowei Wang Mengyan Wang Meilian Cai Rongguang Shao Guimin Xia Wuli Zhao State Key Laboratory of Respiratory Health and Multimorbidity Key Laboratory of Antibiotic BioengineeringMinistry of HealthLaboratory of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Pharmaceutics Department Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Pancreatic cancer is a more aggressive and refractory *** and toxicity limit drug ***,we report a lower toxic and higher effective miriplatin(MPt)-loaded liposome,LMPt,exhibiting totally different anti-cancer mechanism from previously reported platinum *** in gemcitabine(GEM)-resistant/sensitive(GEM-R/S)pancreatic cancer cells,LMPt exhibits prominent anti-cancer activity,led by faster cellular entry-induced larger accumulation of *** level of caveolin-1(Cav-1)determines entry rate and switch of entry pathways of LMPt,indicating a novel role of Cav-1 in nanoparticle *** endosome-lysosome processing,in unchanged metabolite,MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM,to degrade POLG and ***,via PINK1-Parkin axis,mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA(mtDNA)replication ***,POLG and TFAM are identified as novel prognostic markers of pancreatic cancer,and mtDNA replication-induced mitophagy blocking mediates their pro-cancer *** findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA(target of most platinum agents),and totally distinct mechanism of MPt and other formulations of ***-assembly offers LMPt special efficacy and *** action and characteristic mechanism make LMPt a promising cancer candidate.

关键词： Miriplatin-loaded liposome Pancreatic cancer caveolae-mediated endocytosis Caveolin-1 Mitophagy Mitochondria DNA POLG TFAM

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