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

Hernández Pérez, Marta 276 600 0000-0001-6914-9987 Cuscó, Cristina 1cc00d05-7eb6-4394-9e3a-8e0de6170e7a Benítez García, Cristina 154f3305-d2b6-41b6-b586-95950e57e92b Bonelli, Joaquín 81d0bce7-dbf4-44dd-aa7a-0258a11e2451 Nuevo Fonoll, Marina b633c9f2-c176-41c0-8524-4a0974f409b3 Soriano, Aroa 53a9f2d4-adfa-43be-9cff-428080fecaad Martínez García, David 18e02fd6-ef02-4fc0-a41e-ce87d3ba38c1 600 Arias Betancur, Alain 38bb623a-30d8-4c4a-b321-e3d4e5365ce6 García Valverde, María 222 600 0000-0002-3990-8388 Segura, Miguel F. 22b7ce45-57df-4ceb-8c94-37dcecf9790a Quesada Pato, Roberto 458 600 0000-0003-2764-7157 Rocas, Josep 4eb0e8c6-5980-44df-bff3-1dc0675defb4 Soto Cerrato, Vanessa 346bb3c7-0c69-4d62-9045-26b0b8d37a51 600 Pérez Tomás, Ricardo 3306d7a2-706a-47ab-8490-869a1b191c58 600 2024-01-12T13:54:40Z 2024-01-12T13:54:40Z 2021 2227-9059 http://hdl.handle.net/10259/8327 10.3390/biomedicines9050508 2227-9059 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. 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). application/pdf eng MDPI Biomedicines. 2021, V. 9, n. 5, 508 https://doi.org/10.3390/biomedicines9050508 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Polymer nanocapsules Tumor microenvironment PH-tunable Lung cancer treatment Targeted drug delivery systems Amphoteric nanocapsules Medicina Salud Química orgánica Medicine Health Chemistry, Organic Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Biomedicines 9 5 508 THUMBNAIL Hernández-biomedicines_2021.pdf.jpg Hernández-biomedicines_2021.pdf.jpg IM Thumbnail image/jpeg 3555 https://riubu.ubu.es/bitstream/10259/8327/4/Hern%c3%a1ndez-biomedicines_2021.pdf.jpg e8669f32b94e6fcf34788426ffff80e4 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/8327/3/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/8327/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Hernández-biomedicines_2021.pdf Hernández-biomedicines_2021.pdf application/pdf 6340422 https://riubu.ubu.es/bitstream/10259/8327/1/Hern%c3%a1ndez-biomedicines_2021.pdf 31a7664f9da2952700f54c8a40fb6ee1 MD5 1 10259/8327 oai:riubu.ubu.es:10259/8327 2024-01-13 02:05:32.731 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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