纳米药物载体体内命运研究:环境响应型荧光染料的应用  

In vivo fate study of drug nanocarriers: the applications of environment-responsive fluorescent dyes

作　　者：戚建平[1] 卢懿[1] 董肖椿[1] 赵伟利[1] 吴伟[1] QI Jian-ping;LU Yi;DONG Xiao-chun;ZHAO Wei-li;WU Wei(Key Laboratory of Smart Drug Delivery of Ministry of Education,School of Pharmacy,Fudan University,Shanghai 201203,China)

机构地区：[1]复旦大学药学院教育部智能化递药重点实验室

出　　处：《药学学报》2019年第11期1965-1975,共11页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81573363,81872815,81872826,81690263);上海市科技发展基金资助项目(19XD1400300,18410741800)

摘　　要：纳米制剂的体内命运研究关乎其临床转化的成败,目前所面临的最大挑战之一是如何在体内实时准确地监测纳米载体自身。传统的放射或荧光探针从被标记母体粒子解离后,依然发射信号,从而带来干扰,导致对结果的误判。环境响应探针根据纳米载体所处环境变化而切换信号,有助于将粒子信号与游离探针信号有效区分。目前应用的环境响应荧光染料主要有三大类,其原理分别基于荧光共振能量转移(FRET)、聚集诱导发光(AIE)及聚集导致淬灭(ACQ)效应。它们的共同特点是,当被包载于纳米粒中时发射荧光,而伴随着纳米载体的降解或破坏,染料分子被释放,因周围环境变化而发生信号切换或荧光淬灭。根据信号的变化可对纳米粒在生物体内的存续状态进行判断。FRET和AIE染料被广泛用于研究纳米粒和细胞的相互作用,较少应用于体内命运研究。ACQ染料对生物介质中的水敏感,具有普适性,结合各种成像设备,可更为准确地追踪纳米粒在体内的转运过程。本文对3种环境响应荧光染料的应用原理、优缺点及纳米粒体内命运研究中的应用进行了综述。The in vivo fate is a crucial factor that governs the successful translation of nanoformulations.However,one of the current biggest challenges is with the real-time monitoring of the body of the nanoparticles themselves.Conventional radioactive or fluorescent probes give signals even after they are disassociated from the particle matrix,generating interference to bioimaging and leading to misjudgment of results.Environmentresponsive fluorescent dyes are regarded as promising tools due to signal switching in response to the changes in the environment.Currently,there are three categories of dyes in bioimaging of nanoparticles based on Forster resonance energy transfer(FRET),aggregation-induced emission(AIE)and aggregation-caused quenching(ACQ).They have similar characteristics that strong fluorescence is emitted when they are embedded in the matrix of nanocarriers,whereas the fluorescence quenches upon release from the matrix due to dissociation of nanocarriers.The fluorescence switching reflects the existing status of the nanocarriers and therefore helps to interpret the in vivo behaviors.FRET and AIE probes have been widely used in elucidating the interactions between nanoparticles and cell models.However,they show intrinsic defects in studying in vivo fate of nanoparticles.ACQ-based dyes are sensitive to water,a universal factor in the biological environment.Therefore,with the help of bioimaging equipment,the in vivo trafficking process of nanoparticles can be unraveled.This review article tends to provide an overview on the rationale,pros and cons and applications of the three categories of environment-responsive fluorescent dyes in the investigation of the in vivo fate of nanocarriers.

关 键 词：环境响应 荧光染料 聚集导致淬灭 荧光共振能量转移 聚集诱导发光 纳米载体 体内命运 实时监测 

分 类 号：R943[医药卫生—药剂学]