Biodegradable and ph-responsive acetalated dextran (Ac-Dex) nanoparticles for nir imaging and controlled delivery of a platinum-based prodrug into cancer cells

Nanoparticles (NPs) based on the biodegradable acetalated dextran polymer (Ac-Dex) were used for near-infrared (NIR) imaging and controlled delivery of a PtIV prodrug into cancer cells. The Ac-Dex NPs loaded with the hydrophobic PtIV prodrug 3 (PtIV/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 PtIV 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 IC50 values obtained for the PtIV prodrug encapsulated in Ac-Dex NPs were much lower when compared with the IC50 values obtained for the free PtIV 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 therapy16520832094CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP573913/2008-0Não tem2018/02093-0; 2017/06146-8; 2017/24488-3; 08/57906-3The authors gratefully acknowledge Sao Paulo Research Foundation—FAPESP (grant #2018/02093-0 for C.O.; fellowship #2017/06146-8 for C.B.B.; scholarship #2017/24488-3 for G.P.) and Coordination for the Improvement of Higher Education Personnel—CAPES (Ph.D. scholarship for T.B.B.) for the financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior—Brasil (CAPES), finance code 001. We also thank the access to equipment and assistance provided by the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC) at the State University of Campinas; INFABIC is cofunded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) (08/57906-3) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) (573913/2008-0