Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Khlong Luang, Pathum Thani 12120, Thailand.
Int J Biol Macromol. 2020 Nov 1;162:561-577. doi: 10.1016/j.ijbiomac.2020.06.089. Epub 2020 Jun 15.
This study aimed to develop new organic/inorganic nanohybrids of targeted pullulan derivative/gold nanoparticles (FA-PABA-Q188-PUL@AuNPs) to improve the selectivity and efficacy of drugs. The chemical structure of targeted pullulan derivative, folic acid-decorated para-aminobenzoic acid-quat188-pullulan (FA-PABA-Q188-PUL), was designed for reducing, stabilizing, capping, and functionalizing AuNPs. Here, the key factors, including pH, temperature, and FA-PABA-Q188-PUL concentrations, were systematically optimized to control the morphology, size, and functionalization of multifunctional FA-PABA-Q188-PUL@AuNPs. Spherical FA-PABA-Q188-PUL@AuNPs obtained by a green, simple, and bio-inspired strategy under the optimum conditions were thoroughly characterized and had an average size of 12.6 ± 1.5 nm. The anticancer drug DOX was successfully loaded on monodispersed FA-PABA-Q188-PUL@AuNPs and the system exhibited excellent intracellular uptake, specificity, and physicochemical properties. The pH-responsive DOX release from FA-PABA-Q188-PUL@AuNPs-DOX showed fast release (85% after 72 h) under acidic conditions. Furthermore, FA-PABA-Q188-PUL@AuNPs-DOX enhanced the anticancer activity of DOX toward Chago-k1 cancer cells up to 4.8-fold and showed less cytotoxicity toward normal cells than free DOX. The FA-PABA-Q188-PUL@AuNPs-DOX induced the death of cells by increasing late apoptotic cells (26.4%) and arresting the cell cycle at S-G2/M phases. These results showed that innovative FA-PABA-Q188-PUL@AuNPs should be considered as new candidate platforms for anticancer drug delivery systems.
本研究旨在开发新型靶向普鲁兰衍生物/金纳米粒子（FA-PABA-Q188-PUL@AuNPs）有机/无机纳米杂化材料，以提高药物的选择性和疗效。靶向普鲁兰衍生物，即叶酸修饰的对氨基苯甲酸-季铵 188-普鲁兰（FA-PABA-Q188-PUL）的化学结构被设计用于还原、稳定、封端和功能化 AuNPs。在这里，系统优化了包括 pH、温度和 FA-PABA-Q188-PUL 浓度在内的关键因素，以控制多功能 FA-PABA-Q188-PUL@AuNPs 的形态、尺寸和功能化。在最佳条件下，通过绿色、简单和仿生策略获得的球形 FA-PABA-Q188-PUL@AuNPs 经过彻底表征，平均尺寸为 12.6±1.5nm。成功将抗癌药物 DOX 负载到单分散 FA-PABA-Q188-PUL@AuNPs 上，该系统表现出优异的细胞内摄取、特异性和物理化学性质。在酸性条件下，FA-PABA-Q188-PUL@AuNPs-DOX 中的 DOX 呈现出快速释放（72 小时后 85%释放）的 pH 响应性。此外，FA-PABA-Q188-PUL@AuNPs-DOX 增强了 DOX 对 Chago-k1 癌细胞的抗癌活性，达到 4.8 倍，且比游离 DOX 对正常细胞的细胞毒性更小。FA-PABA-Q188-PUL@AuNPs-DOX 通过增加晚期凋亡细胞（26.4%）和将细胞周期阻滞在 S-G2/M 期，诱导细胞死亡。这些结果表明，创新性的 FA-PABA-Q188-PUL@AuNPs 可被视为新型抗癌药物输送系统的候选平台。
