Novel fluorescent pH/reduction dual stimuli-responsive polymeric nanoparticles for intracellular triggered anticancer drug release

• Fluorescent pH/reduction dual-responsive PMPR nanoparticles were designed.
• DOX-loaded PMPR was stable under extracellular conditions with low drug leakage.
• It showed a rapid intracellular drug release in acidic/reductive tumor environment.
• Its strong fluorescence only at low pH media is potential for cancer diagnosis.

Fluorescent poly(methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate-co-N′-rhodamine B-acrylhydrazine) (P(MAA-co-PEGMA-co-RhBAh), PMPR) nanoparticles were designed as pH/reduction dual stimuli-responsive drug delivery system (DDS) for anti-cancer drug via facile distillation-precipitation copolymerization with bio-reducible disulfide-containing crosslinker. As a carrier for doxorubicin (DOX), high drug-loading capacity (DLC) and drug-loading efficiency (DLE) of 53.1% and 97.3% were achieved respectively, via the strong electrostatic interaction between the carboxyl groups of PMAA segments and the amino group of DOX. Due to the disulfide crosslinking structure and their drug-loading mode, the DOX-loaded PMPR nanoparticles were relatively stable under extracellular conditions with low drug leakage, while a rapid intracellular drug release took place in acidic and reductive environment of tumor cells. The fluorescence microscope analysis showed that the DOX-loaded PMPR nanoparticles could be successfully endocytosed by HepG2 cells and the released DOX was mainly accumulated in cell nuclei. These features make them potential DDS for tumor-environment-responsive controlled release. Furthermore, the PMPR nanoparticles showed strong fluorescence only at low pH media, which might be used for the real-time fluorescent imaging in cancer diagnosis as a potential theranostic nanoplatform for imaging-guided therapy of cancer.

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