Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core nanocapsules as a strategy to target Alpha(V) Beta(3) integrin expressed on tumor cells

• Autor(a) principal: Antonow, Michelli Barcelos
• Data de Publicação: 2018
• Outros Autores: Franco, Camila, Prado, Willian Andrade, Beckenkamp, Aline, Silveira, Gustavo Pozza, Buffon, Andreia, Guterres, Silvia Stanisçuaski, Pohlmann, Adriana Raffin
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/182662
• topic: Nanocápsulas de núcleo lipídico; Câncer; Doxorrubicina; Lipid-core nanocapsules; Cancer; RGD; Doxorubicin; Active drug targeting; Surface-functionalization

Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing v 3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of v 3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg mL1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 6 nm, polydispersity index of 0.11 0.04, zeta potential of +13.2 1.9 mV and (6.2 1.1) 1011 particles mL1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 20 and 215 25 nm, 0.10 0.01 and 0.09 0.03, +13.8 2.3 and +16.4 1.5 mV and (6.9 0.6) 1011 and (6.1 1.0) 1011 particles mL1. RGD complexation was 7.73 104 molecules per nanocapsule and Dox loading were 1.51 104 and 7.64 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG.