Abstract
A drug delivery system that is integrated with fluorescent imaging is an emerging platform for tumor diagnostic and therapy. A pH-responsive fluorescent polymer that can respond to the surrounding medium is a desired component with which to construct an advanced drug delivery system with bioimaging characteristics and controllable drug releasing. In this work, we synthesized novel amphiphilic block copolymers of poly(ethylene glycol)-b-poly(2-(diisopropylamino) ethyl methacrylate-co-dithiomaleimide) (PEG-b-poly(DPA-co-DTM)) and poly(ethylene glycol)-b-poly(2-(dibutylamino) ethyl methacrylate-co-dithiomaleimide) (PEG-b-poly(DBA-co-DTM)) with pH-responsiveness and fluorescence. The block copolymers exhibited relatively stable fluorescence properties in different solvent and excitation-independent fluorescence behaviours. By copolymerizing the responsive segments in the molecule chain, the doxorubicin (DOX)-loaded micelles could be triggered to disassemble, thus releasing DOX at the corresponding pH values and yielding a pH-responsive drug release. Targeted deliveries of the drug within the cell were demonstrated by using the carrier responding to different pH values. The best antitumor effect was obtained by PEG-b-poly(DPA-co-DTM), which immediately released DOX as soon as it entered the tumor cells, as a result of responding to the regional pH level (pH = 6.3). The pH-responsive copolymers showed excellent biocompatibilities, as nearly 85% of cells with these fluorescent micelles survive when the testing concentration goes up to 200 μg mL−1. In all, these pH-responsive and dithiomaleimide-based fluorescent block copolymers hold great potential in future cancer diagnostic and therapeutic techniques.
Highlights
Fluorescence imaging, a reliable strategy to detect and visualize bio-subjects both in vitro and in vivo [1,2,3], has led to wide applications in clinical practices [4,5,6,7]
From the perspective of scoping novel materials, the poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) and poly(2-(dibutylamino) ethyl methacrylate) (PDBA) are found to be highly sensitive to pH in early endosomes and late endosomes/lysosomes, which explain their potentials in controlled drug delivery applications [24-29]
We propose a novel fluorescent and pH-responsive material strategy by co-polymerizing fluorescent DTM groups with pH-sensitive polymers (PDPA and PDBA), aiming to improve efficiency for cellular imaging and drug release
Summary
Fluorescence imaging, a reliable strategy to detect and visualize bio-subjects both in vitro and in vivo [1,2,3], has led to wide applications in clinical practices [4,5,6,7]. Combining bioimaging with smart drug release to get multifunctional nanomaterials is of great significance in diagnostic and therapeutic applications [1617]. These imaging-guided drug delivery systems can visualize the accumulation of nanoparticles and simultaneously deliver and trace the drug, thereby evaluating the efficiency of drug delivery [17-18]. From the perspective of scoping novel materials, the poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) and poly(2-(dibutylamino) ethyl methacrylate) (PDBA) are found to be highly sensitive to pH in early endosomes and late endosomes/lysosomes, which explain their potentials in controlled drug delivery applications [24-29]. We propose a novel fluorescent and pH-responsive material strategy by co-polymerizing fluorescent DTM groups with pH-sensitive polymers (PDPA and PDBA), aiming to improve efficiency for cellular imaging and drug release.
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