IL-11Rα-targeted nanostrategy empowers chemotherapy of relapsed and patient-derived osteosarcoma.

Osteosarcoma (OS) is a rare but frequently lethal bone malignancy in children and adolescents. The adjuvant chemotherapy with doxorubicin (Dox) and cisplatin remains a mainstream clinical practice though it affords only limited clinical benefits due to low tumor deposition, dose-limiting toxicity and high rate of relapse/metastasis. Here, taking advantage of high IL-11Rα expression in the OS patients, we installed IL-11Rα specific peptide (sequence: cyclic CGRRAGGSC) onto redox-responsive polymersomes encapsulating Dox (IL11-PDox) to boost the specificity and anti-OS efficacy of chemotherapy. Of note, IL-11Rα peptide at a density of 20% greatly augmented the internalization, apoptotic activity, and migration inhibition of Dox in IL-11Rα-overexpressing 143B OS cells. The active targeting effect of IL11-PDox was supported in orthotopic and relapsed 143B OS models, as shown by striking repression of tumor growth and lung metastasis, and substantial survival benefits over free Dox control. We further verified that IL11-PDox could effectively inhibit patient-derived OS xenografts. IL-11Rα-targeted nanodelivery of chemotherapeutics provides a potential therapeutic strategy for advanced osteosarcoma. [Display omitted] • IL-11Rα is overexpressed in a majority of advanced osteosarcoma (OS) patients. • IL-11Rα specific peptide-polymersome-doxorubicin (IL11-PDox) actively targets OS cells. • IL11-PDox effectively represses OS growth and lung metastasis in orthotopic and relapsed models. • IL11-PDox shows significantly better inhibition of patient-derived OS xenografts than free Dox control. [ABSTRACT FROM AUTHOR]