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Overcoming Doxorubicin Resistance with Lipid-Polymer Hybrid Nanoparticles Photoreleasing Nitric Oxide.
Fraix, Aurore; Conte, Claudia; Gazzano, Elena; Riganti, Chiara; Quaglia, Fabiana; Sortino, Salvatore.
Afiliación
  • Fraix A; Laboratory of Photochemistry, Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, I-95125 Catania, Italy.
  • Conte C; Drug Delivery Laboratory, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, I-80131 Napoli, Italy.
  • Gazzano E; Oncological Pharmacology Laboratory, Department of Oncology, University of Torino, Via Santena 5/bis, I-10126 Torino, Italy.
  • Riganti C; Oncological Pharmacology Laboratory, Department of Oncology, University of Torino, Via Santena 5/bis, I-10126 Torino, Italy.
  • Quaglia F; Drug Delivery Laboratory, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, I-80131 Napoli, Italy.
  • Sortino S; Laboratory of Photochemistry, Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, I-95125 Catania, Italy.
Mol Pharm ; 17(6): 2135-2144, 2020 06 01.
Article en En | MEDLINE | ID: mdl-32286080
We report on tailored lipid-polymer hybrid nanoparticles (NPs) delivering nitric oxide (NO) under the control of visible light as a tool for overcoming doxorubicin (DOX) resistance. The NPs consist of a polymeric core and a coating. They are appropriately designed to entrap DOX in the poly(lactide-co-glycolide) core and a NO photodonor (NOPD) in the phospholipid shell to avoid their mutual interaction both in the ground and excited states. The characteristic red fluorescence of DOX, useful for its tracking in cells, is well preserved upon incorporation within the NPs, even in the copresence of NOPD. The NP scaffold enhances the NO photoreleasing efficiency of the entrapped NOPD when compared with that of the free compound, and the copresence of DOX does not significantly affect such enhanced photochemical performance. Besides, the delivery of DOX and NOPD from NPs is also not mutually influenced. Experiments carried out in M14 DOX-resistant melanoma cells demonstrate that NO release from the multicargo NPs can be finely regulated by excitation with visible light, at a concentration level below the cytotoxic doses but sufficient enough to inhibit the efflux transporters mostly responsible for DOX cellular extrusion. This results in increased cellular retention of DOX with consequent enhancement of its antitumor activity. This approach, in principle, is not dependent on the type of chemotherapeutic used and may pave the way for new treatment modalities based on the photoregulated release of NO to overcome the multidrug resistance phenomenon and improve cancer chemotherapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polímeros / Doxorrubicina / Nanopartículas / Óxido Nítrico Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polímeros / Doxorrubicina / Nanopartículas / Óxido Nítrico Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos