Autor(es):
Lopes-Nunes, Jessica ; Agonia, Ana S. ; Rosado, Tiago ; Gallardo, Eugenia ; Palmeira-de-Oliveira, Rita ; Palmeira-de-Oliveira, Ana ; Martinez-de-Oliveira, José ; Fonseca-Moutinho, José ; Campello, Maria Paula Cabral ; Paiva, Artur ; Paulo, António ; Vulgamott, Alexa ; Ellignton, Andrew D. ; Oliveira, Paula A. ; Cruz, Carla
Data: 2021
Identificador Persistente: https://hdl.handle.net/10316/103807
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): cervical cancer; endometrial carcinoma; acridine orange derivative; Imiquimod; aptamer; gold nanoparticle
Descrição
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.
FCT project ref. IF/00959/2015 financed by Fundo Social Europeu and Programa Operacional Potencial Humano and Project Pessoa 5079/2019. Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016), through national founds and, where applicable, cofinanced by the FEDER through COMPETE 2020, POCI, PORL and PIDDAC. FCT - Post-Doctoral fellowship (Grant SFRH/BPD/124437/2016). UTAustin FCT projectDREAMref. UTAP-EXPL/NTec/0015/2017.
