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Targeted enhancement of flotillin-dependent endocytosis augments cellular uptake and impact of cytotoxic drugs.
Fekri, Farnaz; Abousawan, John; Bautista, Stephen; Orofiamma, Laura; Dayam, Roya M; Antonescu, Costin N; Karshafian, Raffi.
Afiliación
  • Fekri F; Department of Chemistry and Biology, Ryerson University, Toronto, Canada.
  • Abousawan J; Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, M5B 2K3, Canada.
  • Bautista S; Department of Chemistry and Biology, Ryerson University, Toronto, Canada.
  • Orofiamma L; Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, M5B 2K3, Canada.
  • Dayam RM; Department of Chemistry and Biology, Ryerson University, Toronto, Canada.
  • Antonescu CN; Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, M5B 2K3, Canada.
  • Karshafian R; Department of Chemistry and Biology, Ryerson University, Toronto, Canada.
Sci Rep ; 9(1): 17768, 2019 11 28.
Article en En | MEDLINE | ID: mdl-31780775
Cellular uptake is limiting for the efficacy of many cytotoxic drugs used to treat cancer. Identifying endocytic mechanisms that can be modulated with targeted, clinically-relevant interventions is important to enhance the efficacy of various cancer drugs. We identify that flotillin-dependent endocytosis can be targeted and upregulated by ultrasound and microbubble (USMB) treatments to enhance uptake and efficacy of cancer drugs such as cisplatin. USMB involves targeted ultrasound following administration of encapsulated microbubbles, used clinically for enhanced ultrasound image contrast. USMB treatments robustly enhanced internalization of the molecular scaffold protein flotillin, as well as flotillin-dependent fluid-phase internalization, a phenomenon dependent on the protein palmitoyltransferase DHHC5 and the Src-family kinase Fyn. USMB treatment enhanced DNA damage and cell killing elicited by the cytotoxic agent cisplatin in a flotillin-dependent manner. Thus, flotillin-dependent endocytosis can be modulated by clinically-relevant USMB treatments to enhance drug uptake and efficacy, revealing an important new strategy for targeted drug delivery for cancer treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Sistemas de Liberación de Medicamentos / Microburbujas / Endocitosis / Proteínas de la Membrana / Antineoplásicos Límite: Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisplatino / Sistemas de Liberación de Medicamentos / Microburbujas / Endocitosis / Proteínas de la Membrana / Antineoplásicos Límite: Humans Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido