Multi-Responsive Polypeptidosome: Characterization, Morphology Transformation, and Triggered Drug Delivery

• Published in: Macromolecular rapid communications. 2014-10, Vol.35 (19), p.1673-1678
• Main Authors: Liu, Gang, Zhou, Linzhu, Guan, Yanfei, Su, Yue, Dong, Chang-Ming
• Format: Article
• Language: English
• Subjects: Aminoacid polymers; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Applied sciences; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Drug Carriers; Drug delivery systems; Drugs; Exact sciences and technology; HeLa Cells; Humans; Morphology; nanomedicine; Nanostructure; Oxidation-Reduction; Peptides - chemistry; Physicochemistry of polymers; polymeric vesicle; polypeptide; Polypeptides; Stimuli; stimuli-responsive polymer; Synthetic biopolymers; Transformations; triggered drug release
• ISSN: 1022-1336; 1521-3927
• DOI: 10.1002/marc.201400343

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 H2O2 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 H2O2 trigger. A novel multi‐responsive polypeptide‐based vesicle (polypeptidosome) is fabricated by controlling the structure transformation of one polypeptide block copolymer, and it presents the combined sensitivity of multiple physiological and clinic‐related stimuli. The anticancer drug doxorubicin can be released in a controlled or on–off manner, enabling the polypeptidosome useful for on‐demand nanomedicine and cancer therapy.