cRGD targeted and charge conversion-controlled release micelles for doxorubicin delivery

Efficiently and selectively delivering chemotherapeutic agents to tumours still remains a challenge for the development of nanocarriers. In this study, polymer micelles based on cRGD targeting and pH-sensitive surface charge-switching were successfully prepared and used for doxorubicin (Dox) delivery. This nanoscale polymeric micelle indicated a high drug encapsulation efficiency of 90% and slightly negative charge. Drug release experiments showed a pH-enhanced release profile in PBS, which resulted from surface charge-switching by imidazole. Confocal laser scanning microscopy and flow cytometry experiments indicated that combining the capability of an RGD target and pH-sensitive charge-switching significantly enhanced the cellular uptake of B16F10 cells overexpressing alpha(v)beta(3) integrins. An MTT assay also showed that our hybrid RGD-decorated micelles were much more cytotoxic to B16F10 cells than undecorated micelles. These results suggest the potential application of a cRGD target and pH-sensitive surface charge-switching polymeric micelles in the treatment of alpha(v)beta(3) integrin-overexpressing cancers.