PDF(Pubmed)
Abstract：
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 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\'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.
摘要：
人乳头瘤病毒（HPV）相关的宫颈癌是全球女性中最常见的癌症。治疗选择与女性不孕症的增加密切相关。咪喹莫特（IQ）是一种咪唑并喹啉，已证明，通过在载体中配制时通过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，像纳米凝胶，局部使用。常规疗法的有效替代是纳米颗粒药物递送系统。我们研究了具有IQ（LipoIQ）的脂质纳米颗粒，并用DNA适体对其进行了功能化，AT11（LipoIQAT11），以提高对宫颈癌细胞的选择性结合精油的功效。该制剂显示物理化学性质足以用于阴道药物递送并且在较高浓度下具有抗微生物活性(MIC50从0.625%开始)。最终的制剂在癌细胞中表现出细胞毒性，通过精油增强而不影响健康细胞，导致HeLa细胞中小于10%的细胞活力和NHDF细胞中超过60%。精油增强LipoIQ的有效性，而AT11增加了对宫颈癌细胞的选择性。正如渗透测定的结果表明，这些制剂被癌细胞内化。总的来说,获得的结果表明，精油和纳米系统的协同作用增强了LipoIQ的细胞毒性作用，LipoIQAT11增强了对癌细胞的选择性。
