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Temozolomide (TMZ), although the main chemotherapeutic agent used, shows limited efficacy due to low solubility, chemical instability, and acquired resistance. In this context, nanostructured systems can enhance their antitumor efficacy. This study aimed to develop and characterize chitosan-functionalized nanostructured lipid carriers loaded with Temozolomide (NLCTQ), as well as to assess their biological activity in human glioblastoma cells (U87-MG). Lipid nanoparticles functionalized with chitosan were prepared by hot emulsification and sonication. Physicochemical characterization included DLS, zeta potential, FTIR, and HPLC for drug quantification and encapsulation efficiency. Biological activity was evaluated in U87-MG cells using the cell viability assay MTT and trypan blue, the comet assay, the spheroid model, fluorescence cell death, and the CBMN assay. The formulation presented a homogeneous nanometric size and positive zeta potential, although with moderate encapsulation efficiency (39%). Biological assays demonstrated that NLCTQ significantly reduced cell viability, overcoming the U87-MG cell line\u2019s resistance to TMZ by achieving cytotoxicity at doses up to 20 times lower than free TMZ. Additionally, NLCTQ promoted the formation of biomarkers of chromosomal instability, such as micronuclei, bridges, and nuclear buds, which may explain the observed cytotoxic effects. Together, the results indicate that TMZ nanoencapsulation in NLCTQ enhances its antitumor efficacy, representing a promising strategy to overcome the limitations of conventional chemotherapy in glioblastoma treatment.<\/jats:p>","DOI":"10.1007\/s00210-026-05365-y","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T02:49:30Z","timestamp":1777258170000},"page":"15395-15414","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and characterization of chitosan-functionalized nanostructured lipid carriers with temozolomide: cytotoxic effects and chromosomal instability in human glioblastoma cells"],"prefix":"10.1007","volume":"399","author":[{"given":"Helber Alves","family":"Negreiros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro Alves Damaceno","family":"do Lago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Alves","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia Raquel Alves","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina Lima","family":"de Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Gabriel Barbosa","family":"de Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson","family":"da Cruz Esteves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio Eduardo Matos Cazarotti","family":"Francisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Lemos","family":"Paiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro Crispim Guerra","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Medeiros Martins","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Henricke Oliveira","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Fl\u00e1via Chaves","family":"Uch\u00f4a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny Leticia Marinho Ramos","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleska Fernanda","family":"de Alencar Sales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria H\u00e9rika","family":"da Silva Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidiane","family":"de Lima Feitoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalton Dittz","family":"J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Cavalcanti Carneiro","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Humberto","family":"Xavier-J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Michel Pinheiro","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Marcelo","family":"de Castro e Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"5365_CR1","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.jconrel.2020.02.020","volume":"321","author":"M Agrawal","year":"2020","unstructured":"Agrawal M et al (2020) Recent strategies and advances in the fabrication of nano lipid carriers and their application towards brain targeting. 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