Legumain-triggered aggregable gold nanoparticles for enhanced intratumoral retention  

作　　者：Zhi Li Wenpei Li Shaoping Jiang Chuan Hu Yuanyu Huang Maxim Shevtsov Huile Gao Shaobo Ruan 

机构地区：[1]Advanced Research Institute of Multidisciplinary Sciences,School of Life Science,Beijing Institute of Technology,Beijing 100081,China [2]Key Laboratory of Drug Targeting and Drug Delivery System,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [3]Institute of Cytology of Russian Academy of Sciences(RAS),St.Petersburg 194064,Russia

出　　处：《Chinese Chemical Letters》2024年第7期388-393,共6页中国化学快报（英文版）

基　　金：supported by the Beijing Natural Science Foundation(No.L222128);Beijing Institute of Technology Research Fund Program for Young Scholars(No.XSQD-202121010);National Natural Science Foundation of China(No.81961138009)。

摘　　要：Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed legumain.The aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral retention.In vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain expression.In vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral injection.More importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 tumor.The effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.

关 键 词：LEGUMAIN Size-tunable Enhanced retention Stimulus-responsive NANOMEDICINE 

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