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Perfluorocarbon Nanoemulsions for Combined Pulmonary siRNA Treatment of Lung Metastatic Osteosarcoma
Author(s) -
Li Zhaoting,
Shen Yuexin,
Wang Yixin,
Zhu Lianghan,
Zhu Chenfei,
Qian Chenggen,
Sun Minjie,
Oupicky David
Publication year - 2019
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201900039
Subject(s) - osteosarcoma , lung , cancer research , medicine , stat3 , stat protein , metastasis , tumor microenvironment , pathology , immunology , chemistry , cancer , signal transduction , tumor cells , biochemistry
Lung metastatic osteosarcoma is a lethal disease afflicting children and adolescents, with a 5‐year survival rate of less than 20%. The development of perfluorocarbon (PFC) nanoemulsions as systems for direct pulmonary delivery of combination drug/siRNA therapy is reported. Fluorinated polycation (F‐PCX) with an inherent ability to inhibit C‐X‐C receptor type 4 (CXCR4) is synthesized and used as a surfactant in the preparation of F‐PCX@PFC nanoemulsions. The nanoemulsions are loaded with siRNA against signal transducer and activator of transcription 3 (STAT3) for combined treatment of lung metastasis in osteosarcoma. Intratracheal instillation of the treatments significantly prolonged the survival of animals with established lung metastases. The treatment with F‐PCX@PFC/siSTAT3 emulsion polyplexes decreased the number of myeloid‐derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the tumors, while increasing CD8 + T cells infiltration and IFNγ secretion to overcome the immunosuppressive tumor microenvironment. The reported nanoemulsions represent a promising pulmonary treatment of lung metastatic osteosarcoma.