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

doi:10.1039/c8sc01069b

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy
	Yan, Chenxu 2; Guo, Zhiqian 2; Shen, Yanyan 1; Chen, Yi1 ; Tian, He 2; Zhu, Wei-Hong 2
刊名	CHEMICAL SCIENCE
	2018-06-14
卷号	9 期号:22 页码:4959-4969
ISSN号	2041-6520
DOI	10.1039/c8sc01069b
文献子类	Article
英文摘要	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.
资助项目	NSFC/China[21788102] ; NSFC/China[21421004] ; NSFC/China[21636002] ; NSFC/China[21622602] ; National key Research and Development Program[2016YFA0200300] ; Oriental Scholarship, Scientific Committee of Shanghai[14ZR1409700] ; Oriental Scholarship, Scientific Committee of Shanghai[15XD1501400] ; Shanghai Pujiang Program[13PJD010] ; Fok Ying Tong Education Foundation[142014] ; Fundamental Research Funds for the Central Universities[WK1013002] ; Programme of Introducing Talents of Discipline to Universities[B16017] ; NIH[85-23]
WOS关键词	TARGETED DRUG-DELIVERY ; NEAR-INFRARED EMISSION ; CANCER-THERAPY ; FLUORESCENT-PROBE ; RATIONAL DESIGN ; NANOPARTICLES ; RELEASE ; CELLS ; CHEMOSENSORS ; NANOCARRIERS
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000434693300005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279707]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Guo, Zhiqian; Zhu, Wei-Hong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.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;
推荐引用方式 GB/T 7714	Yan, Chenxu,Guo, Zhiqian,Shen, Yanyan,et al. Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy[J]. CHEMICAL SCIENCE,2018,9(22):4959-4969.
APA	Yan, Chenxu,Guo, Zhiqian,Shen, Yanyan,Chen, Yi,Tian, He,&Zhu, Wei-Hong.(2018).Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy.CHEMICAL SCIENCE,9(22),4959-4969.
MLA	Yan, Chenxu,et al."Molecularly precise self-assembly of theranostic nanoprobes within a single-molecular framework for in vivo tracking of tumor-specific chemotherapy".CHEMICAL SCIENCE 9.22(2018):4959-4969.