Abstract：
The incidence of head and neck cancers, particularly those associated with Human Papillomavirus (HPV) infections, has been steadily increasing. Conventional therapies exhibit limitations and drawbacks, prompting the exploration of new strategies over the years, with nanomedicine approaches, especially liposomes gaining relevance. Additionally, the functionalization of liposomes with aptamers enables selective delivery to target cells. For instance, AT11 can serve as a targeting moiety for cancer cells due to its high affinity for nucleolin, a protein overexpressed on the cancer cell\'s surface. In this study, liposomes functionalized with AT11 are proposed as drug delivery systems for imiquimod (IQ), aiming to maximize its potential as an anticancer agent for HPV-related cancers. To this end, firstly liposomes were produced through the ethanol injection method, functionalized with AT11-TEG-Cholesteryl, and characterized using dynamic light scattering. The obtained liposomes presented suitable properties for cancer therapy (with sizes from 120 to 140 nm and low polydispersity PDI < 0.16) and were further evaluated in terms of potential anticancer effects. AT11 IQ-associated liposomes allowed a selective delivery of IQ towards a tongue cancer cell line (UPCI-SCC-154) relative to the non-malignant cell line (Het1A). Specifically, they induced a selective reduction of the cell viability (∼52 % versus ∼113 %; p < 0.0001), proliferation (∼68 % versus ∼102 %; p<0.0001) and increased cell death (∼7-fold increase; p < 0.0001)). Additionally, they decreased the migration (from ∼24 % to ∼8 %; p < 0.0001) and invasion (to 11 %; p = 0.0047) capacities of the cancer cells. In summary, the produced liposomes represent a promising approach to enhance the anticancer potential of IQ in head and neck cancer, particularly in tongue cancer.
摘要：
头颈癌的发病率,特别是与人乳头瘤病毒（HPV）感染相关的那些，一直在稳步增长。常规疗法表现出局限性和缺点，多年来推动新战略的探索，用纳米医学方法，尤其是脂质体获得相关性。此外,脂质体与适体的功能化使得能够选择性递送至靶细胞。例如,由于AT11对核仁素的高亲和力，它可以作为癌细胞的靶向部分，一种在癌细胞表面过度表达的蛋白质。在这项研究中,用AT11功能化的脂质体被提议作为咪喹莫特（IQ）的药物递送系统，旨在最大限度地发挥其作为HPV相关癌症的抗癌药物的潜力。为此,首先通过乙醇注射法制备脂质体，用AT11-TEG-胆固醇酯官能化，并使用动态光散射进行表征。所获得的脂质体呈现用于癌症治疗的合适性质(具有120至140nm的尺寸和低多分散性PDI<0.16),并且在潜在的抗癌作用方面进一步评估。相对于非恶性细胞系（Het1A），AT11IQ相关脂质体允许向舌癌细胞系（UPCI-SCC-154）选择性递送IQ。具体来说,它们诱导了细胞活力的选择性降低(~52%对~113%；p<0.0001)，增殖(68%对102%；p<0.0001)和细胞死亡增加(~7倍增加；p<0.0001))。此外,它们降低了癌细胞的迁移能力(从24%到8%；p<0.0001)和侵袭能力(到11%；p=0.0047)。总之,所产生的脂质体代表了一种有希望的方法来增强IQ在头颈部癌症中的抗癌潜力，尤其是舌癌。
