Bryaskova Rayna, Georgiev Nikolai, Philipova Nikoleta, Bakov Ventsislav, Anichina Kameliya, Argirova Maria, Apostolova Sonia, Georgieva Irina, Tzoneva Rumiana
Department of Polymer Engineering, University of Chemical Technology and Metallurgy, 8 Kliment Ohridsky Str., 1756 Sofia, Bulgaria.
Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridsky Str., 1756 Sofia, Bulgaria.
Pharmaceutics. 2023 Jun 16;15(6):1753. doi: 10.3390/pharmaceutics15061753.
Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 μM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.
开发了具有新型抗癌药物控释功能的荧光胶束载体，以实现细胞内成像和癌症治疗的同步进行。基于通过原子转移自由基聚合（ATRP）获得的两亲性聚（丙烯酸）-嵌段-聚（丙烯酸正丁酯）（PAA-b-PnBA）共聚物和疏水性抗癌苯并咪唑腙药物（BzH）的自组装行为，将纳米级荧光胶束系统嵌入新型抗癌药物。通过这种方法，由于疏水相互作用，获得了由亲水性PAA壳和嵌入BzH药物的疏水性PnBA核组成的明确的纳米级荧光胶束，从而达到了非常高的包封效率。分别使用动态光散射（DLS）、透射电子显微镜（TEM）和荧光光谱研究了空白和载药胶束的尺寸、形态和荧光特性。此外，孵育72小时后，载药胶束释放出3.25μM的BzH，通过分光光度法测定。发现载有BzH药物的胶束对MDA-MB-231细胞表现出增强的抗增殖和细胞毒性作用，对微管组织具有持久作用，具有凋亡改变并优先定位在癌细胞的核周空间。相比之下，单独的BzH或掺入胶束中的BzH对非癌细胞MCF-10A的抗肿瘤作用相对较弱。
