{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:53:40Z","timestamp":1784307220649,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo de Investigaci\u00f3n sobre Salud y Cerveza de M\u00e9xico, A. C. Fomento a la Investigaci\u00f3n","award":["110-19"],"award-info":[{"award-number":["110-19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>A glioblastoma is an aggressive form of a malignant glial-derived tumor with a poor prognosis despite multimodal therapy approaches. Lactate has a preponderant role in the tumor microenvironment, playing an immunoregulatory role as well as being a carbon source for tumor growth. Lactate homeostasis depends on the proper functioning of intracellular lactate regulation systems, such as transporters and enzymes involved in its synthesis and degradation, with evidence that an intracellular lactate overload generates metabolic stress on tumor cells and tumor cell death. We propose that the delivery of a lactate overload carried in nanoparticles, allowing the intracellular release of lactate, would compromise the survival of tumor cells. We synthesized and characterized silica and titania nanoparticles loaded with lactate to evaluate the cellular uptake, metabolic activity, pH modification, and cytotoxicity on C6 cells under normoxia and chemical hypoxia, and, finally, determined the survival of an orthotopic malignant glioma model after in situ administration. A dose-dependent reduction in metabolic activity of treated cells under normoxia was found, but not under hypoxia, independent of glucose concentration. Lactated-loaded silica nanoparticles were highly cytotoxic (58.1% of dead cells) and generated significant supernatant acidification. In vivo, lactate-loaded silica nanoparticles significantly increased the median survival time of malignant glioma-bearing rats (p = 0.005) when administered in situ. These findings indicate that lactate-loaded silica nanoparticles are cytotoxic on glioma cells in vitro and in vivo.<\/jats:p>","DOI":"10.3390\/pharmaceutics14020327","type":"journal-article","created":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:12:56Z","timestamp":1643501576000},"page":"327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Lactate-Loaded Nanoparticles Induce Glioma Cytotoxicity and Increase the Survival of Rats Bearing Malignant Glioma Brain Tumor"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2961-9187","authenticated-orcid":false,"given":"V\u00edctor","family":"Chavarria","sequence":"first","affiliation":[{"name":"Neuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"},{"name":"Laboratorio de Inmunorregulaci\u00f3n, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Ortiz-Islas","sequence":"additional","affiliation":[{"name":"Nanotechnology Laboratory, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alel\u00ed","family":"Salazar","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8754","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"P\u00e9rez-de la Cruz","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behaviour Laboratory, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Espinosa-Bonilla","sequence":"additional","affiliation":[{"name":"Central de Instrumentaci\u00f3n, Posgrado en Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"},{"name":"Laboratorio de Inmunorregulaci\u00f3n, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8466-1505","authenticated-orcid":false,"given":"Alma","family":"Ort\u00edz-Plata","sequence":"additional","affiliation":[{"name":"Experimental Neuropathology Laboratory, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Sotelo","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunorregulaci\u00f3n, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-312X","authenticated-orcid":false,"given":"Benjam\u00edn","family":"Pineda","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurolog\u00eda y Neurocirug\u00eda (INNN), Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Vleeschouwer, S. 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