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Treatment of recurrent or advanced cervical cancer is still limited, and new therapeutic choices are needed for improving prognosis and quality of life of patients. Because human papilloma virus ( HPV ) infection is critical in cervical carcinogenesis, with the  E6  and  E7  oncogenes of  HPV  degrading tumor suppressor proteins through the ubiquitin proteasome system, the inhibition of the ubiquitin proteasome system appears to be an ideal target to suppress the growth of cervical tumors. Herein, we focused on the ubiquitin proteasome inhibitor  MG 132 (carbobenzoxy‐Leu‐Leu‐leucinal) as an anticancer agent against cervical cancer cells, and physically incorporated it into micellar nanomedicines for achieving selective delivery to solid tumors and improving its  in vivo  efficacy. These  MG 132‐loaded polymeric micelles ( MG 132/m) showed strong tumor inhibitory  in vivo  effect against  HPV ‐positive tumors from HeLa and CaSki cells, and even in  HPV ‐negative tumors from C33A cells. Repeated injection of  MG 132/m showed no significant toxicity to mice under analysis by weight change or histopathology. Moreover, the tumors treated with  MG 132/m showed higher levels of tumor suppressing proteins,  hS crib and p53, as well as apoptotic degree, than tumors treated with free  MG 132. This enhanced efficacy of  MG 132/m was attributed to their prolonged circulation in the bloodstream, which allowed their gradual extravasation and penetration within the tumor tissue, as determined by intravital microscopy. These results support the use of  MG 132 incorporated into polymeric micelles as a safe and effective therapeutic strategy against cervical tumors.

Enhanced efficacy against cervical carcinomas through polymeric micelles physically incorporating the proteasome inhibitor MG 132