Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells

SIMPLE SUMMARY: Gynecologic cancers are a major concern since they can significantly affect women’s lives. Moreover, the available therapeutic options increase the risk of infertility. Thus, better treatment options for women with these pathologies represent an urgent need. The DNA G-quadruplex aptamer AS1411 covalently conjugated to gold nanoparticles presents high selectivity to cancer cells and can be used as a drug delivery system for anticancer drugs. By using these AS1411-functionalized nanoparticles we aimed to improve the anticancer effect of two molecules with promising effects that can be improved. After the supramolecular conjugation of AS1411-gold nanoparticles with the molecules, we were able to overcome the lack of selectivity in the case of a potential anticancer ligand (C(8)) and improve the anticancer effect of a commercially available drug (Imiquimod). Overall, with the resulting nanoparticles the benefits of both drugs were significantly improved in gynecologic cancer cells. ABSTRACT: Cervical cancer is one of the most common cancers and is one of the major cause of deaths in women, especially in underdeveloped countries. The patients are usually treated with surgery, radiotherapy, and chemotherapy. However, these treatments can cause several side effects and may lead to infertility. Another concerning gynecologic cancer is endometrial cancer, in which a high number of patients present a poor prognosis with low survival rates. AS1411, a DNA aptamer, increases anticancer therapeutic selectivity, and through its conjugation with gold nanoparticles (AS1411-AuNPs) it is possible to improve the anticancer effects. Therefore, AS1411-AuNPs are potential drug carriers for selectively delivering therapeutic drugs to cervical cancer. In this work, we used AS1411-AuNPs as a carrier for an acridine orange derivative (C(8)) or Imiquimod (IQ). The AS1411 aptamer was covalently bound to AuNPs, and each drug was associated via supramolecular assembly. The final nanoparticles presented suitable properties for pharmaceutical applications, such as small size, negative charge, and favorable drug release properties. Cellular uptake was characterized by confocal microscopy and flow cytometry, and effects on cellular viability were determined by MTT assay. The nanoparticles were then incorporated into a gel formulation of polyethylene glycol, suitable for topical application in the female genital tract. This gel showed promising tissue retention properties in Franz cells studies in the porcine vaginal epithelia. These findings suggest that the tested nanoparticles are promising drug carriers for cervical cancer therapy.