文献类型：期刊文献

英文题名：Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy

作者：Yan, Chenxu[1];Guo, Zhiqian[1];Shen, Yanyan[2];Chen, Yi[2];Tian, He[1];Zhu, Wei-Hong[1]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai Key Lab Funct Mat Chem, Key Lab Adv Mat,Inst Fine Chem, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China

年份：2018

卷号：9

期号：22

起止页码：4959

外文期刊名：CHEMICAL SCIENCE

收录：;EI(收录号：20182405299607);WOS:【SCI-EXPANDED(收录号:WOS:000434693300005)】；

基金：This work was supported by the NSFC/China (21788102, 21421004, 21636002 and 21622602), National key Research and Development Program (2016YFA0200300), Oriental Scholarship, Scientific Committee of Shanghai (14ZR1409700 and 15XD1501400), Shanghai Pujiang Program (13PJD010), Fok Ying Tong Education Foundation (142014), Fundamental Research Funds for the Central Universities (WK1013002), and Programme of Introducing Talents of Discipline to Universities (B16017). This study was performed in strict accordance with the NIH guidelines for the care and use of laboratory animals (NIH Publication No. 85-23 Rev. 1985) and was approved by the Institutional Animal Care and Use Committee of National Tissue Engineering Center (Shanghai, China).

语种：英文

外文关键词：Cancer cells - Controlled drug delivery - Diseases - Chemotherapy - Mammals - Self assembly - Drug products - Hydrophilicity - Micelles - Coenzymes - Lanthanum compounds - Sulfur compounds - Targeted drug delivery - Critical micelle concentration - Infrared devices

摘要：Structural heterogeneity and the lack of in vivo real-time tracking of drug release are the utmost barriers for nanocarrier-mediated prodrugs in targeted therapy. Herein, we describe the strategy of molecularly precise self-assembly of monodisperse nanotheranostics for BPn-DCM-S-CPT (n = 0, 5 and 20) with fixed drug loadings (36%, 23% and 16%) and constant release capacities, permitting in vivo real-time targeted therapy. We focus on regulating the hydrophilic fragment length to construct stable, well-defined nanostructured assemblies. Taking the bis-condensed dicyanomethylene-4H-pyran (DCM) derivative as the activatable near-infrared (NIR) fluorophore, it makes full use of two terminal conjunctions: the hydrophobic disulfide-bridged anticancer prodrug camptothecin (CPT) and the hydrophilic oligomer-bridged biotin segment serving as an active targeting unit. From the rational design, only BP20-DCM-SCPT forms uniform and highly stable self-assemblies (ca. 80 nm, critical micelle concentration = 1.52 mu M) with several advantages, such as structural homogeneity, fixed drug loading efficiency, real-time drug release tracking and synergistic targeting (passive, active and activatable ability). More importantly, in vitro and in vivo experiments verify that the surface-grafted biotins of nanoassemblies are directly exposed to receptors on cancer cells, thus markedly facilitating cellular internalization. Notably, through synergistic targeting, BP20-DCM-S-CPT displays excellent tumor-specific drug release performance in HeLa tumor-bearing nude mice, which has significantly enhanced in vivo antitumor activity and nearly eradicates the tumor (IRT = 99.7%) with few side effects. For the first time, the specific molecularly precise self-assembly of BP20-DCM-S-CPT within a single-molecular framework has successfully achieved a single reproducible entity for real-time reporting of drug release and cancer therapeutic efficacy in living animals, providing a new insight into amphiphilic nanotheranostics for clinical translation.