Real-time monitoring of a controlled drug delivery system in vivo: construction of a near infrared fluorescence monomer conjugated with pH-responsive polymeric micelles†
Abstract
Real-time monitoring of drug delivery systems has attracted growing interest for potential applications in biomedical therapy. Fluorescence imaging is a highly sensitive technique for illuminating the pathways of such systems. In this work, we designed and synthesized a new near infrared (NIR) fluorescent dye monomer (NFM). The NFM monomer was covalently attached to a pH-responsive amphiphilic block copolymer by reversible addition–fragmentation chain transfer (RAFT) copolymerization using hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) as the macro-RAFT agent and pH-responsive 2-(4-(dodecyloxy)phenyl)-1,3-dioxan-5-yl methacrylate (DBAM) and NFM as the comonomer, to synthesize the multifunctional amphiphilic block copolymer PPEGMA-b-P(DBAM-co-NFM) with NIR moieties and pH-sensitive groups. The PPEGMA-b-P(DBAM-co-NFM) could be self-assembled easily into stable micelles with doxorubicin (DOX) with an average diameter of 66 nm in water. The nano-size of the micelles is suitable for cycling through the body and carrying drugs to tumor sites safely via the enhanced permeability and retention (EPR) effect. Confocal laser scanning microscopy (CLSM) results indicated cells’ uptake and the intracellular distribution. In vivo imaging of the micelles was observed in real time and the fluorescent signals clearly demonstrated the dynamic process of tumor treatment. This versatile and effective strategy is a potential tool for monitoring controlled drug delivery for tumor treatment.