A pH-sensitive polymeric nanovesicle based on biodegradable poly(ethylene glycol)-b-poly(2-(diisopropylamino)ethyl aspartate) as a MRI-visible drug delivery system

Abstract

Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable 2-(diisopropylamino)ethanol grafted poly(L-aspartic acid) (PAsp(DIP)) were synthesized and evaluated as a MRI-visible and pH-sensitive drug delivery system. The copolymers can self-assemble into stable vesicles in aqueous solutions at neutral pH, resembling the physiological environment, whereas they disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. The anticancer drug doxorubicin (DOX) and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated inside the inner aqueous core of the vesicles for cancer therapy and MR imaging, respectively. In vitrodrug release studies showed that the DOX release from the pH-sensitive vesicles was significantly faster at pH 5.0 than at pH 7.4. SPIONs clustering inside the inner aqueous core of the vesicles resulted in a high spin–spin (T₂) relaxivity. Cell culture studies showed that the DOX-SPION-loaded vesicles could be effectively internalized by human hepatic cancer Bel 7402 cells, and DOX could be rapidly released from vesicles inside lysosomal compartments and then migrated into nuclei. Consequently effective suppression of cancer cell growth was detected. This study demonstrated the potential of the biodegradable DOX-SPION-loaded pH-sensitive vesicles as an effective multifunctional nanomedicine platform for cancer therapy due to their pH-triggerable drug release and high MRI sensitivity.