Redox and pH Dual-Responsive Polymeric Micelles with Aggregation-Induced Emission Feature for Cellular Imaging and Chemotherapy

Abstract

Intelligent polymeric micelles for antitumor drug delivery and tumor bioimaging have drawn a broad attention because of their reduced systemic toxicity, enhanced efficacy of drugs, and potential application of tumor diagnosis. Herein, we developed a multifunctional polymeric micelle system based on a pH and redox dual-responsive mPEG-P(TPE- co-AEMA) copolymer for stimuli-triggered drug release and aggregation-induced emission (AIE) active imaging. These mPEG-P(TPE- co-AEMA)-based micelles showed excellent biocompatibility and emission property, exhibiting great potential application for cellular imaging. Furthermore, the antitumor drug doxorubicin (DOX) could be encapsulated during self-assembly process with high loading efficiency, and a DOX-loaded micelle system with a size of 68.2 nm and narrow size distribution could be obtained. DOX-loaded micelles demonstrated great tumor suppression ability in vitro, and the dual-responsive triggered intracellular drug release could be further traced. Moreover, DOX-loaded micelles could efficiently accumulate at the tumor site because of enhanced permeability and retention effect and long circulation of micelles. Compared with free DOX, DOX-loaded micelles exhibited better antitumor effect and significantly reduced adverse effects. Given the efficient accumulation targeting to tumor tissue, dual-responsive drug release, and excellent AIE property, this polymeric micelle would be a potential candidate for cancer therapy and diagnosis.

Luminescent core–shell nanoparticles with crosslinked aggregation‐induced emission core structures: Emission both in solution and solid states

“…Tetraphenylethylene (TPE) is one of the representative AIE structures and a variety of TPE‐based AIE materials have been developed for chemosensing, bioimaging, optoelectronics, and stimuli‐responsive applications . For example, Wang and coworkers have developed the redox and pH dual‐responsive polymer micelles with TPE structure for cellular imaging and chemotherapy . Further, Tang et al have achieved metal ion detection using TPE‐containing polymers .…”

“…[10][11][12][13][14] For example, Wang and coworkers have developed the redox and pH dual-responsive polymer micelles with TPE structure for cellular imaging and chemotherapy. [15] Further, Tang et al have achieved metal ion detection using TPE-containing polymers. [16] Solvatochromic characteristics of molecules with TPE and benzothiadiazole (BTz) structures have been investigated in detail by Misra et al [17] Although AIE-based materials are practically interesting as discussed earlier, the emission property of AIE materials still depends on molecular dispersion as well as conventional luminescent materials.…”

Development of a Non‐Coding‐RNA‐based EMT/CSC Inhibitory Nanomedicine for In Vivo Treatment and Monitoring of HCC

“…Sci. [43][44][45][46]48] We developed a folate-conjugated nanocarrier (FaPPS) that achieved the in vivo delivery of therapeutic nucleic acid into hepatoma cells successfully in our previous study. [43][44][45][46] Decoration with specific ligands or antibodies [47] enables nanomedicines to recognize molecular signatures on the cell membrane for high efficiency in vivo recognition of cancer cells.…”

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

“…Recently, intelligent micelles have been designed to be stimulus‐sensitive, such as redox‐, temperature‐, pH‐ and specific enzyme‐dependent responses for targeted delivery . Zhuang et al developed a redox and pH dual‐responsive micelle system to deliver doxorubicin. They synthesized an amphiphilic polymer with AIE attributes ( 15 , Figure ) which can self‐assemble into micelles.…”