Maocha Izamara, Rosado Beatriz, Lopes-Nunes Jéssica, Lopes Melanie, Rolo Joana, Pires Bruno, Gallardo Eugénia, Palmeira-de-Oliveira Ana, Martinez-de-Oliveira José, Palmeira de Oliveira Rita, Medeiros Rui, Cruz Carla
CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal.
Labfit-Health Products Research and Development Lda, UBIMedical, 6200-284 Covilhã, Portugal.
Pharmaceutics. 2024 Jun 27;16(7):864. doi: 10.3390/pharmaceutics16070864.
Human papillomavirus (HPV)-associated cervical cancer is the most common cancer among women worldwide. 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 MIC 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's 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.
人乳头瘤病毒(HPV)相关宫颈癌是全球女性中最常见的癌症。治疗方案与女性不孕症增加密切相关。咪喹莫特(IQ)是一种咪唑喹啉,当它以纳米凝胶等载体形式配制用于局部使用时,已被证明通过Toll样受体7/8激活免疫细胞,对持续性HPV感染具有抗病毒作用。纳米颗粒药物递送系统是传统疗法的一种有效替代方案。我们研究了负载IQ的脂质纳米颗粒(Lipo IQ),并用DNA适配体AT11对其进行功能化(Lipo IQ AT11),以提高对宫颈癌细胞的选择性,并结合精油的功效。这些制剂表明其物理化学性质适合阴道给药,并且在较高浓度下具有抗菌活性(最低抑菌浓度从0.625%开始)。最终制剂在癌细胞中表现出细胞毒性,精油可增强这种毒性,同时不影响健康细胞,导致HeLa细胞的细胞活力低于10%,而NHDF细胞的细胞活力超过60%。精油增强了Lipo IQ的有效性,而AT11提高了对宫颈癌细胞的选择性。渗透试验结果表明,这些制剂被癌细胞内化。总体而言,所得结果表明精油和纳米系统的协同作用增强了Lipo IQ的细胞毒性作用,并且Lipo IQ AT11促进了对癌细胞的选择性。
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