Multi-responsive polypeptidosome: characterization, morphology transformation, and triggered drug delivery.

The biodegradable polymeric nanomedicines that may be integrated with multi-stimuli-sensitivity to achieve triggered or on-demand drug release kinetics are challenging for polymer therapeutics and drug delivery systems. By controlling the structure transformation of one polypeptide-b-PEO copolymer, a novel multi-responsive polypeptide-based vesicle (polypeptidosome) presents the combined sensitivity of multiple physiological and clinic-related stimuli, and both morphology and size of the polypeptidosome are changed during the triggered process. The designer polypeptide has unique structures composed of 1) light-responsive o-nitrobenzyl groups, 2) oxidizable thioether linkers, 3) photo-caged redox thiol groups on parent poly(L-cysteine), and 4) tunable conformation, which enable the polypeptidosome to have a peculiar multi-response. The anticancer drug doxorubicin can be released in a controlled or on-off manner. The combination stimuli of UV irradiation and H2 O2 oxidation induces a large effect and a lower IC50 of 3.80 μg doxorubicin (DOX) equiv/mL compared to 5.28 μg DOX equiv/mL of individual H2 O2 trigger.