Tiwari Sanjay, Sarolia Jayant, Kansara Vrushti, Chudasama Nishith A, Prasad Kamalesh, Ray Debes, Aswal Vinod K, Bahadur Pratap
Maliba Pharmacy College, Gopal-Vidyanagar Campus, Uka Tarsadia University, Surat 394350, India.
Natural Products & Green Chemistry Division, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364002, India.
Polymers (Basel). 2020 Oct 1;12(10):2258. doi: 10.3390/polym12102258.
This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14-20 nm) which remained stable against temperature (ca. 25-45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π-π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.
本研究报道了在α-生育酚聚乙二醇琥珀酸酯（TPGS）与氨基苯硼酸（APBA）共价功能化后开发的可靶向胶束。核磁共振（NMR）和红外（IR）光谱结果表明APBA成功连接到TPGS的亲水性片段上。动态光散射和小角中子散射研究表明，该共轭物在水中自组装形成球形核壳胶束（14 - 20 nm），在温度（约25 - 45°C）和pH值变化时保持稳定。这些胶束可以溶解高负载量的紫杉醇（PLX），且平均尺寸无变化。然而，在饱和溶解度下，药物分子从核迁移到壳区域，并通过π-π堆积相互作用与APBA基团结合。共聚焦显微镜和细胞分选分析证实了TPGS-APBA胶束在表达唾液酸（SA）的MDA-MB-453细胞中的有效转运能力。在等效PLX剂量下，TPGS-APBA胶束在暴露2小时的细胞中凋亡死亡显示出约两倍的改善。我们的研究结果表明，APBA的连接可能是一种改善在表达SA残基的癌细胞中载体细胞内定位的潜在策略。
