文献类型：期刊文献

英文题名：Real-time near-infrared bioimaging of a receptor-targeted cytotoxic dendritic theranostic agent

作者：Wu, Junchen;Zhou, Yuren;Li, Shang;Qu, Dahui;Zhu, Wei-Hong[1];Tian, He

机构：[1]East China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China; East China Univ Sci & Technol, Collaborat Innovat Ctr Coal Based Energy iCCE, Shanghai Key Lab Funct Mat Chem, Inst Fine Chem,Sch Chem & Mol Engn, Shanghai 200237, Peoples R China

年份：2017

卷号：120

起止页码：1

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20170103222801);WOS:【SCI-EXPANDED(收录号:WOS:000394398900001)】；

基金：We thank the National Basic Research 973 Program (2013CB733700), and NSFC for Creative Research Groups (21421004) and Distinguished Young Scholars (21325625), NSFC/China, Shanghai Sci. & Tech. and Edu. Committee (15XD1501400), the Fundamental Research Funds for the Central Universities (WJ1213007 and WJ1416005), and Programme of Introducing Talents of Discipline to Universities (B16017) for financial support.

语种：英文

外文关键词：Substance P; 5-fluorouracil; Neurokinin-1 receptor; Near-infrared imaging; Anticancer

摘要：Efficient and site-specific delivery of anticancer drugs to tumors is important, in the development of effective cancer chemotherapy. As an undecapeptide of the tachykinin neuropeptide family, the substance P (SP)/neurokinin-1 receptor (NK1R) system has been identified as a promising ligand-receptor pair in tumor-specific drug delivery. However, the rational design of suitable theranostic agents with high drug loading capacity and tumor targeting for cancer patients remains a great challenge. Herein, we report a dendritic strategy that utilizes the two amine functionalities of lysine to create branch points that allow conjugation of the anticancer drug 5-fluorouracil (5-FU) to the tumor-targeting ligand substance P, along with an additional near-infrared (NIR) squaraine dye, to construct a theranostic dendritic agent, P-FU 4. This cytotoxic theranostic agent, containing four carboxyl-modified 5-FU molecules, has several desirable advantages: i) the ability to self-assemble into nanoparticles; ii) enhanced cytotoxicity with high drug loading capacity (16%) and a specific receptor-targeted interaction with NK1R through the SP moiety; and iii) a high NIR squaraine fluorescence efficiency due to the specific dendron isolation, avoiding aggregation-mediated quenching. As demonstrated in this report, the cytotoxic activity of P-FU 4 is dose-dependent against the tested cancer cells. The improved drug loading capacity with dendritic branching distinctly enhanced cytotoxicity to tumor cells but had little effect on the viability of normal cells. P-FU 4 was preferentially taken up by tumor cells through a receptor-mediated interaction, which was monitored by effective NIR fluorescence with high tissue penetration. Studies using a mouse model revealed that P-FU 4 can significantly inhibit tumor progression, with a tumor-inhibition rate of 60.2%. The receptor-targeted cytotoxic dendritic theranostic agent is highly preferable to standard chemotherapeutic treatments and decreases the negative side effects of medications on healthy cells, which establishes its utility in drug delivery and cancer chemotherapy. (C) 2016 Elsevier Ltd. All rights reserved.