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The treatment options are strongly related to increased infertility in women. Imiquimod (IQ) is an imidazoquinoline, which has proven antiviral effects against persistent HPV infection by activating immune cells via Toll-like receptors 7\/8 when formulated in carriers, like nanogels, for topical use. An effective alternative to conventional therapies is the nanoparticle drug delivery system. We studied lipidic nanoparticles with IQ (Lipo IQ) and functionalized them with a DNA aptamer, AT11 (Lipo IQ AT11), to improve the selectivity for cervical cancer cells combined with the efficacy of essential oils. The formulations showed that the physicochemical properties are adequate for vaginal drug delivery and have antimicrobial activity at higher concentrations (with MIC50 starting from 0.625%). The final formulations exhibited cytotoxicity in cancer cells, enhanced by essential oils without affecting healthy cells, resulting in less than 10% cell viability in HeLa cells and over 60% in NHDF cells. Essential oils potentiate Lipo IQ\u2019s effectiveness, while AT11 increases the selectivity for cervical cancer cells. As suggested by the results of the permeation assay, the formulations were internalized by the cancer cells. Overall, the obtained results suggested that the synergistic effect of the essential oils and the nanosystem potentiate the cytotoxic effect of Lipo IQ and that Lipo IQ AT11 promotes selectivity towards cancer cells.<\/jats:p>","DOI":"10.3390\/pharmaceutics16070864","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T03:42:30Z","timestamp":1719546150000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Imiquimod-Loaded Nanosystem for Treatment Human Papillomavirus-Induced Lesions"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2403-7022","authenticated-orcid":false,"given":"Izamara","family":"Maocha","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Beatriz","family":"Rosado","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"J\u00e9ssica","family":"Lopes-Nunes","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Melanie","family":"Lopes","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5291-212X","authenticated-orcid":false,"given":"Joana","family":"Rolo","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4181-9130","authenticated-orcid":false,"given":"Bruno","family":"Pires","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-8998","authenticated-orcid":false,"given":"Eug\u00e9nia","family":"Gallardo","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Ana","family":"Palmeira-de-Oliveira","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Labfit\u2013Health Products Research and Development Lda, UBIMedical, 6200-284 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Jos\u00e9","family":"Martinez-de-Oliveira","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9311-8355","authenticated-orcid":false,"given":"Rita","family":"Palmeira de Oliveira","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Labfit\u2013Health Products Research and Development Lda, UBIMedical, 6200-284 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-1242","authenticated-orcid":false,"given":"Carla","family":"Cruz","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Departamento de Qu\u00edmica, Universidade da Beira Interior, 6201-001 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, X., Huang, X., and Zhang, Y. 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