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

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Nano Research 2023年第5期16卷 7422-7430页

作者： Weiyue Ban Qiuhua Luo Chengda Yan Xiaoying Fan Guorui Zhu Maosheng Cheng Zhonggui He Mengchi Sun Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy The First Hospital of China Medical UniversityShenyang 110001China Phase I Clinical Trials Center The First Hospital of China Medical UniversityShenyang 110102China Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

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 *** albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular *** 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 *** 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

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