A boronic acid conjugation integrates antitumor drugs into albumin-binding prodrugs-based nanoparticles with robust efficiency for cancer therapy  

作　　者：Weiyue Ban Qiuhua Luo Chengda Yan Xiaoying Fan Guorui Zhu Maosheng Cheng Zhonggui He Mengchi Sun Jin Sun 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Department of Pharmacy,The First Hospital of China Medical University,Shenyang 110001,China [3]Phase I Clinical Trials Center,The First Hospital of China Medical University,Shenyang 110102,China [4]Key Laboratory of Structure-Based Drug Design and Discovery,Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,China [5]School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Nano Research》2023年第5期7422-7430,共9页纳米研究（英文版）

基　　金：the National Key Research and Development Program of China(No.2021YFA0909900);the National Natural Science Foundation of China(Nos.82073777 and 81803442);the General Project of Liaoning Provincial Department of Education(Nos.LJKZ0927 and LJKQZ2021034);the Natural Science Foundation of Liaoning Province(No.2022-BS-157).

摘　　要：Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.

关 键 词：drug delivery Abraxane® albumin-based paclitaxel nanoparticles phenylboronic acid group antitumor nanomedicines 

分 类 号：R730.5[医药卫生—肿瘤]