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

Autor(es)

Braga, Carolyne B. ^[1] ; Perli, Gabriel ^[1] ; Becher, Tiago B. ^[1] ; Omelas, Catia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil

• 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
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/02093-0 - Desenvolvimento de novos nanomateriais para aplicações em nanomedicina
• Beneficiário: Cátia Cristina Capêlo Ornelas Megiatto
• Modalidade de apoio: 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
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado