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

适体功能化的金纳米粒子用于向妇科癌细胞输送药物

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作者:Jessica Lopes-Nunes, Ana S Agonia, Tiago Rosado, Eugénia Gallardo, Rita Palmeira-de-Oliveira, Ana Palmeira-de-Oliveira, José Martinez-de-Oliveira, José Fonseca-Moutinho, Maria Paula Cabral Campello, Artur Paiva, António Paulo, Alexa Vulgamott, Andrew D Ellignton, Paula A Oliveira, Carla Cruz

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 (C8) 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.

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