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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Biodegradable and pH-Responsive Acetalated Dextran (Ac-Dex) Nanoparticles for NIR Imaging and Controlled Delivery of a Platinum-Based Prodrug into Cancer Cells

Texto completo
Autor(es):
Braga, Carolyne B. [1] ; Perli, Gabriel [1] ; Becher, Tiago B. [1] ; Omelas, Catia [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: MOLECULAR PHARMACEUTICS; v. 16, n. 5, p. 2083-2094, MAY 2019.
Citações Web of Science: 0
Resumo

Nanoparticles (NPs) based on the biodegradable acetalated dextran polymer (Ac-Dex) were used for near-infrared (NIR) imaging and controlled delivery of a Pt-IV prodrug into cancer cells. The Ac-Dex NPs loaded with the hydrophobic Pt(IV)prodrug 3 (Pt-IV/Ac-Dex NPs) and with the novel hydrophobic NIR-fluorescent dye 9 (NIR-dye 9/Ac-Dex NPs), as well as Ac-Dex NPs coloaded with both compounds (coloaded Ac-Dex NPs), were assembled using a single oil-in-water nanoemulsion method. Dynamic light scattering measurements and scanning electron microscopy images showed that the resulting Ac-Dex NPs are spherical with an average diameter of 100 nm, which is suitable for accumulation in tumors via the enhanced permeation and retention effect. The new nanosystems exhibited high drug-loading capability, high encapsulation efficiency, high stability in physiological conditions, and pH responsiveness. Drug-release studies clearly showed that the Pt(IV)prodrug 3 release from Ac-Dex NPs was negligible at pH 7.4, whereas at pH 5.5, this compound was completely released with a controlled rate. Confocal laser scanning microscopy unambiguously showed that the NIR-dye 9/Ac-Dex NPs were efficiently taken up by MCF-7 cells, and cytotoxicity assays against several cell lines showed no significant toxicity of blank Ac-Dex NPs up to 1 mg mL(-1). The IC(50 )values obtained for the Pt(IV)prodrug encapsulated in Ac-Dex NPs were much lower when compared with the IC50 values obtained for the free Pt(IV)complex and cisplatin in all cell lines tested. Overall, our results demonstrate, for the first time, that Ac-Dex NPs constitute a promising drug delivery platform for cancer therapy. (AU)

Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
Beneficiário:Hernandes Faustino de Carvalho
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 18/02093-0 - Desenvolvimento de novos nanomateriais para aplicações em nanomedicina
Beneficiário:Cátia Cristina Capêlo Ornelas Megiatto
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/24488-3 - Desenvolvimento de carregadores nanoestruturados baseados em polisacarídeos para entrega controlada de antibióticos e nanopartículas de prata
Beneficiário:Gabriel Perli
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 17/06146-8 - Desenvolvimento de nanocarregadores baseados em dendrímeros e nanopartículas poliméricas para a vetorização seletiva da goniotalamina, piplartina e monastrol
Beneficiário:Carolyne Brustolin Braga
Linha de fomento: Bolsas no Brasil - Pós-Doutorado