Perfluorocarbon Nanoemulsions for Combined Pulmonary siRNA Treatment of Lung Metastatic Osteosarcoma

Zhaoting Li, Yuexin Shen, Yixin Wang, Lianghan Zhu, Chenfei Zhu, Chenggen Qian, Minjie Sun, David Oupicky

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1900039
JournalAdvanced Therapeutics
Volume2
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • CXCR4
  • STAT3
  • nanoemulsion
  • osteosarcoma lung metastasis
  • perfluorocarbon

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Pharmaceutical Science
  • Genetics(clinical)
  • Biochemistry, medical
  • Pharmacology (medical)

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