2026-04-17T17:50:25Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/83272024-01-13T01:05:32Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925

00925njm 22002777a 4500 dc Hernández Pérez, Marta author Cuscó, Cristina author Benítez García, Cristina author Bonelli, Joaquín author Nuevo Fonoll, Marina author Soriano, Aroa author Martínez García, David author Arias Betancur, Alain author García Valverde, María author Segura, Miguel F. author Quesada Pato, Roberto author Rocas, Josep author Soto Cerrato, Vanessa author Pérez Tomás, Ricardo author 2021 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. 2227-9059 http://hdl.handle.net/10259/8327 10.3390/biomedicines9050508 2227-9059 Polymer nanocapsules Tumor microenvironment PH-tunable Lung cancer treatment Targeted drug delivery systems Amphoteric nanocapsules Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug