RT info:eu-repo/semantics/article
T1 Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
A1 Hernández Pérez, Marta
A1 Cuscó, Cristina
A1 Benítez García, Cristina
A1 Bonelli, Joaquín
A1 Nuevo Fonoll, Marina
A1 Soriano, Aroa
A1 Martínez García, David
A1 Arias Betancur, Alain
A1 García Valverde, María
A1 Segura, Miguel F.
A1 Quesada Pato, Roberto
A1 Rocas, Josep
A1 Soto Cerrato, Vanessa
A1 Pérez Tomás, Ricardo
K1 Polymer nanocapsules
K1 Tumor microenvironment
K1 PH-tunable
K1 Lung cancer treatment
K1 Targeted drug delivery systems
K1 Amphoteric nanocapsules
K1 Medicina
K1 Medicine
K1 Salud
K1 Health
K1 Química orgánica
K1 Chemistry, Organic
AB Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.
PB MDPI
SN 2227-9059
YR 2021
FD 2021
LK http://hdl.handle.net/10259/8327
UL http://hdl.handle.net/10259/8327
LA eng
NO We thank CERCA Programme/Generalitat de Catalunya for institutional support. M.P.-H. thanks “La Caixa foundation” for her postdoctoral fellowship. A.A. thanks PFCHA/Becas Chile (Folio #72200156). D.M.G. thanks the Government of Catalonia for his predoctoral fellowship through L’Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR; FI-DRG 2016).
DS Repositorio Institucional de la Universidad de Burgos
RD 23-nov-2024