Antonow Michelli B, Franco Camila, Prado Willian, Beckenkamp Aline, Silveira Gustavo P, Buffon Andréia, Guterres Sílvia S, Pohlmann Adriana R
Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000 RS, Brazil.
Nanomaterials (Basel). 2017 Dec 22;8(1):2. doi: 10.3390/nano8010002.
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 αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL (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) × 10 particles mL, 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) × 10 and (6.1 ± 1.0) × 10 particles mL. 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.
阿霉素（Dox）的临床应用因剂量相关的心肌病而受到限制，随着累积剂量的增加，这种情况越来越普遍。此前，我们开发了载有阿霉素的脂质核纳米胶囊（Dox-LNC），在本研究中，我们假设自组装和界面反应可用于获得精氨酰甘氨酰天冬氨酸（RGD）表面功能化的Dox-LNC，其可靶向过表达αvβ3整合素的肿瘤细胞。我们研究了表达不同水平αvβ3整合素的人乳腺腺癌细胞系（MCF-7）和人胶质母细胞瘤星形细胞瘤（U87MG）。用100和500 mg·mL的阿霉素制备了RGD功能化的Dox-LNC（RGD-MCMN（Dox100）和RGD-MCMN（Dox500））。空白制剂（RGD-MCMN）的平均粒径为162±6 nm，多分散指数为0.11±0.04，ζ电位为+13.2±1.9 mV，颗粒浓度为(6.2±1.1)×10个/mL，而RGD-MCMN（Dox100）和RGD-MCMN（Dox500）的平均粒径分别为146±20和215±25 nm，多分散指数分别为0.10±0.01和0.09±0.03，ζ电位分别为+13.8±2.3和+16.4±1.5 mV，颗粒浓度分别为(6.9±0.6)×10和(6.1±1.0)×10个/mL。每个纳米胶囊的RGD络合量为7.73×10⁴个分子，每个纳米胶囊的阿霉素负载量分别为1.51×10⁴和7.64×10⁴个分子。RGD功能化的纳米胶囊对U87MG细胞具有更高的摄取能力。帕累托图显示，在MCF-7和U87MG中，细胞活力主要受阿霉素浓度和处理时间的影响。RGD功能化对细胞活力的影响仅是U87MG的一个决定性因素。
