Decoration of squalenoyl-gemcitabine nanoparticles with squalenyl-hydroxybisphosphonate for the treatment of bone tumors

Therapeutic perspectives of bone tumors such as osteosarcoma remain restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancer squalene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was syn...

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Detalles Bibliográficos
Autores: Rodríguez-Nogales, Carlos, Desmaële, Didier, Sebastián, Víctor, Couvreur, Patrick, Blanco-Prieto, María J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/265597
Acceso en línea:http://hdl.handle.net/10261/265597
https://doi.org/10.1002/cmdc.202100464
Access Level:acceso abierto
Descripción
Sumario:Therapeutic perspectives of bone tumors such as osteosarcoma remain restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancer squalene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bisphosphonate moiety to the squalene chain. This amphiphilic compound was inserted onto squalenoyl-gemcitabine nanoparticles using the nanoprecipitation method. The co-assembly led to nanoconstructs of 75 nm, with different morphology and colloidal properties. The presence of squalenyl-hydroxybisphosphonate enhanced the nanoparticles binding affinity for hydroxyapatite, a mineral present in the bone. Moreover, the in vitro anticancer activity was preserved when tested in commercial and patient-treated derived pediatric osteosarcoma cells. Further in vivo studies will shed light on the potential of these nanomedicines for the treatment of bone sarcomas.