Biostable and bioreducible polymersomes for intracellular delivery of doxorubicin
To minimize the premature drug release of nanocarriers, we have developed chemically cross-linked bioreducible polymersomes (CLPMs) that can specifically release the drug inside cancer cells. Polymersomes were prepared using poly(ethylene glycol)-b-poly(lysine)-b-poly(caprolactone), a biocompatible triblock copolymer. To chemically cross-link the polymersomes, the primary amine of the triblock copolymer was reacted with a disulfide-containing cross-linker. Doxorubicin (DOX) was chosen as a model anti-cancer drug, and was effectively encapsulated into the CLPMs. The drug-loaded polymersomes greatly retarded the release of DOX under physiological conditions (pH 7.4), whereas the release rate of DOX increased remarkably in the presence of 10 mM glutathione, mimicking an intracellular environment. Microscopic observation showed that DOX-loaded CLPMs could effectively deliver the drug into an intracellular level of SCC7 cancer cells, leading to high cytotoxicity. These observations suggest that CLPMs are promising nanocarriers for intracellular DOX delivery.