Stimuli-responsive hybrid cluster bombs of PEGylated chitosan encapsulated DOX-loaded superparamagnetic nanoparticles enabling tumor-specific disassembly for on-demand drug delivery and enhanced MR imaging

Facile approach was established to fabricate the hybrid cluster bombs of PEGylated chitosan encapsulated doxorubicin (DOX)-loaded superparamagnetic nanoparticles as tumor-specific theranostics for targeted DOX delivery and magnetic resonance (MR) imaging, by simply co-precipitation of poly(ethylene glycol) modified chitosan (CS-PEG), oleylamine modified Fe 3 O 4 (OA-Fe 3 O 4 ) nanoparticles and DOX. In presence of OA-Fe 3 O 4 , the particle size of the DOX/OA-Fe 3 O 4 @CS-PEG cluster bombs decreased to around 80 nm from 300 nm of the DOX/CS-PEG nanoparticles, with high drug-loading capacity (DLC) of 24.3% and saturation magnetization (Ms) of 4.11 emu/g, respectively. The in vitro evaluation results indicated that the blank OA-Fe 3 O 4 @CS-PEG clusters showed excellent cytocompatibility, while the DOX/OA-Fe 3 O 4 @CS-PEG clusters could be uptaken into HepG2 cells to deliver DOX into the cell nuclei with enhanced anti-cancer efficacy in comparison with free DOX. In the tumor intracellular micro-environment, the stimuli-responsive hybrid cluster bombs disassembled and re-self-assembled into the OA-Fe 3 O 4 nanoparticle clusters with higher Ms for MR imaging-guided diagnosis, owing to the tumor-specific DOX release and dissolution of CS-PEG.