Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

Autor(es)

Antonow, Michelli B. ^[1] ; Franco, Camila ^[2] ; Prado, Willian ^[3] ; Beckenkamp, Aline ^[2] ; Silveira, Gustavo P. ^[3] ; Buffon, Andreia ^[2] ; Guterres, Silvia S. ^[2] ; Pohlmann, Adriana R. ^{[2, 1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Nanotecnol Farmaceut, Ave Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[2] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Ciencias Farmaceut, Ave Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[3] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim Organ, Ave Bento Goncalves 9500, BR-91501970 Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NANOMATERIALS; v. 8, n. 1 JAN 2018.
• Citações Web of Science: 2

Resumo

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 alpha v beta 3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of alpha v beta 3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mgmL(-1) (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) x 10(11) particles mL(-1), 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) x 10(11) and (6.1 +/- 1.0) x 10(11) particles mL(-1). RGD complexation was 7.73 x 10(4) molecules per nanocapsule and Dox loading were 1.51 x 10(4) and 7.64 x 10(4) 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. (AU)

• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático