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Poly(L-glutamic acid)-cisplatin nanoformulations with detachable PEGylation for prolonged circulation half-life and enhanced cell internalization

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Bioactive Materials 2021年第9期6卷 2688-2697页

作者： Zhongyu Jiang Xiangru Feng Haoyang Zou Weiguo Xu Xiuli Zhuang Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun130022P.R.China School of Applied Chemistry and Engineering University of Science and Technology of China96 Jinzhai RoadHefei230026P.R.China

PEGylation has been widely applied to prolong the circulation times of nanomedicines via the steric shielding effect,which consequently improves the intratumoral ***,cell uptake of PEGylated nanoformulations is always blocked by the steric repulsion of PEG,which limits their therapeutic *** this end,we designed and prepared two kinds of poly(L-glutamic acid)-cisplatin(PLG-CDDP)nanoformulations with detachable PEG,which is responsive to specific tumor tissue microenvironments for prolonged circulation time and enhanced cell *** extracellular pH(pHe)-responsive cleavage 2-propionic-3-methylmaleic anhydride(CDM)-derived amide bond and matrix metalloproteinases-2/9(MMP-2/9)-sensitive degradable peptide PLGLAG were utilized to link PLG and PEG,yielding pHe-responsive PEG-pHe-PLG and MMP-sensitive *** corresponding smart nanoformulations PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were then prepared by the complexation of polypeptides and cisplatin(CDDP).The circulation half-lives of PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were about 4.6 and 4.2 times higher than that of the control PLG-Pt,*** reaching tumor tissue,PEG on the surface of nanomedicines was detached as triggered by pHe or MMP,which increased intratumoral CDDP retention,enhanced cell uptake,and improved antitumor efficacy toward a fatal high-grade serous ovarian cancer(HGSOC)mouse model,indicating the promising prospects for clinical application of detachable PEGylated nanoformulations.

关键词： Poly(L-glutamic acid) Detachable PEGylation Prolonged circulation time Enhanced cell uptake platinum chemotherapy

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BRCA mutated pancreatic cancer:A change is coming

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World Journal of Gastroenterology 2021年第17期27卷 1943-1958页

作者： Michael N Rosen Rachel A Goodwin Michael M Vickers Faculty of Medicine The University of OttawaOttawa K1H 8L6OntarioCanada The Ottawa Hospital Cancer Center The University of OttawaOttawa K1H 8L6OntarioCanada

Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced ***,patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast *** BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8%of patients with sporadic pancreatic *** patients with germline BRCA mutations,platinum-based chemotherapies and poly(ADP-ribose)polymerase inhibitors are effective treatment options which may offer survival *** review will focus on the molecular biology,epidemiology,and management of BRCA-mutated pancreatic ***-more,we will discuss future directions for this area of research and promising active areas of research.

关键词： Pancreatic cancer Systemic therapy platinum chemotherapy BRCA Deoxyribonucleic acid repair Poly(ADP-ribose)polymerase inhibitors

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