{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:31:28Z","timestamp":1787160688287,"version":"build-2736575974"},"reference-count":90,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01007"],"award-info":[{"award-number":["PI19\/01007"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005053","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina","doi-asserted-by":"publisher","award":["CB06\/01\/0026"],"award-info":[{"award-number":["CB06\/01\/0026"]}],"id":[{"id":"10.13039\/501100005053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Gobierno de Arag\u00f3n","doi-asserted-by":"publisher","award":["T57_17R"],"award-info":[{"award-number":["T57_17R"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Gobierno de Arag\u00f3n","doi-asserted-by":"publisher","award":["B054\/12"],"award-info":[{"award-number":["B054\/12"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic\u00ae F127 hybrid dendritic\u2013linear\u2013dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2\u2032-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2\u2032-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously.<\/jats:p>","DOI":"10.3390\/ijms22105223","type":"journal-article","created":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T23:17:16Z","timestamp":1621207036000},"page":"5223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Combination Chemotherapy with Cisplatin and Chloroquine: Effect of Encapsulation in Micelles Formed by Self-Assembling Hybrid Dendritic\u2013Linear\u2013Dendritic Block Copolymers"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-6645","authenticated-orcid":false,"given":"Rebeca","family":"Gonz\u00e1lez-Pastor","sequence":"first","affiliation":[{"name":"Grupo de Terapia G\u00e9nica y Celular, Instituto Aragon\u00e9s de Ciencias de la Salud (IACS\/IIS-Aragon), 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-9186","authenticated-orcid":false,"given":"Alexandre","family":"Lancelot","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Organica, Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC\u2014University of Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Morcuende-Ventura","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Organica, Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC\u2014University of Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-9456","authenticated-orcid":false,"given":"Mar\u00eda","family":"San Anselmo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Organica, Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC\u2014University of Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7091-077X","authenticated-orcid":false,"given":"Teresa","family":"Sierra","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Organica, Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC\u2014University of Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Organica, Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC\u2014University of Zaragoza, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-7846","authenticated-orcid":false,"given":"Pilar","family":"Martin-Duque","sequence":"additional","affiliation":[{"name":"Grupo de Terapia G\u00e9nica y Celular, Instituto Aragon\u00e9s de Ciencias de la Salud (IACS\/IIS-Aragon), 50009 Zaragoza, Spain"},{"name":"Fundaci\u00f3n Araid, 50018 Zaragoza, Spain"},{"name":"Network of Biomedical Research Centers for Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029 Madrid, Spain"},{"name":"Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd2683","article-title":"Mechanisms of drug combinations: Interaction and network perspectives","volume":"8","author":"Jia","year":"2009","journal-title":"Nat. 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