Reduction-responsive polypeptide nanomedicines significantly inhibit progression of orthotopic osteosarcoma.
Nanomedicine. 2019 Aug 20;:102085
Authors: Yin F, Wang Z, Jiang Y, Zhang T, Wang Z, Hua Y, Song Z, Liu J, Xu W, Xu J, Cai Z, Ding J
Osteosarcoma (OS) is the most common malignant bone tumor with high metastasis and mortality. Neoadjuvant chemotherapy is an effective therapeutic regimen, but the clinical application is limited by the unsatisfactory efficacies and considerable side effects. In this study, the reduction-responsive polypeptide micelles based on methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (mPEG113-b-PBMLC4, P4M, and mPEG113-b-PBMLC9, P9M) were developed to control the delivery of doxorubicin (DOX) in OS therapy. Compared to free DOX, P4M/DOX and P9M/DOX exhibited 2.6 and 3.5 times increases in the area under the curve (AUC) of pharmacokinetics, 1.6 and 2.0 times increases in tumor accumulation, and 1.6 and 1.7 times decreases the distribution in the heart. Moreover, the selective accumulation of micelles, especially P9M/DOX, in tumors induced stronger antitumor effects on both primary and lung metastatic OSs with less systematic toxicity. These micelles with smart responsiveness to intracellular microenvironments are highly promising for the targeted delivery of clinical chemotherapeutic drugs in cancer therapy.
PMID: 31442580 [PubMed – as supplied by publisher]