PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA–docetaxel conjugates  

作　　者：Tao Liu Hui Zou Jingqing Mu Xi Zhang Guohua Liu Na Yu Bo Yuan Xiaoyong Yuan Xingjie Liang Shutao Guo 

机构地区：[1]Key Laboratory of Functional Polymer Materials of Ministry of Education,State Key Laboratory of Medicinal Chemical Biology,Institute of Polymer Chemistry,College of Chemistry,Nankai University,Tianjin 300071,China [2]School of Medicine,Nankai University,Tianjin 300071,China [3]Clinical College of Ophthalmology,Tianjin Medical University,Tianjin 300020,China [4]Tianjin Key Laboratory of Ophthalmology and Visual Science,Tianjin Eye Institute,Tianjin Eye Hospital,Tianjin 300020,China [5]CAS Center for Excellence in Nanoscience,CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,Chinese Academy of Sciences and National Center for Nanoscience and Technology of China,Beijing 100190,China

出　　处：《Chinese Chemical Letters》2023年第9期225-229,共5页中国化学快报（英文版）

基　　金：financially supported by National Natural Science Foundation of China(Nos.32171386 and 32201157);the Natural Science Foundation of Tianjin of China(No.21JCZDJC01250);the China Postdoctoral Science Foundation(No.2021M690793)。

摘　　要：Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs,but suffers from poor compatibility between drugs and nanocarriers.Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines.However,the influence of hydrophobic length on the performance of this type of nanomedicine is little known.Here we synthesized two acid-sensitive ketal-linked mPEG-PDLLA–docetaxel prodrugs with different lengths of PDLLA,and engineered them into self-assembled sub-20 nm micellar nanomedicines for breast cancer chemotherapy.We found that the nanomedicine consisting of a mPEG-PDLLA–docetaxel prodrug with the shorter length of PDLLA stood out due to its potent cytotoxicity,deep penetration into multicellular spheroids,and improved in vivo anticancer performance.Additionally,our prodrug-based nanomedicines outperformed the generic formulation of commercial Nanoxel in terms of safety profile,tolerated doses,and tumor suppression.Our findings indicate that the hydrophobic content of a polymeric prodrug nanomedicine plays an important role in the performance of the nanomedicine,and should be instructive for developing polymeric prodrug-based nanomedicines with clinical translational potential.

关 键 词：NANOMEDICINE PRODRUG DOCETAXEL mPEG-PDLLA Acid-sensitive 

分 类 号：TQ460.1[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程]