Subramaniam Bavani, Arshad Norhafiza M, Malagobadan Sharan, Misran Misni, Nyamathulla Shaik, Mun Kein Seong, Nagoor Noor Hasima
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
Centre for Research in Biotechnology for Agriculture (CEBAR), University of Malaya, Kuala Lumpur 50603, Malaysia.
Pharmaceutics. 2021 Mar 24;13(4):439. doi: 10.3390/pharmaceutics13040439.
1'-acetoxychavicol acetate (ACA) extracted from the rhizomes of Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.
从莪术（姜科）根茎中提取的1'-乙酰氧基查维醇醋酸酯（ACA）已被证明可在多种癌症类型中失调NF-κB信号通路并诱导凋亡介导的细胞死亡。然而，ACA是一种疏水性酯，在水性介质中的溶解度差，生物利用度有限，且在体内靶向性不明确。为了解决这些问题，将ACA包裹在锚定八盐酸普勒克索（AMD3100）的纳米结构脂质载体（NLC）中，以促进向表达C-X-C趋化因子受体4（CXCR4）的前列腺癌细胞的靶向递送。采用熔融和高剪切均质法制备NLC，其表现出理想的物理化学性质、成功的包封和修饰以及持续的药物释放速率。此外，它在体外对PC-3细胞表现出基于时间的、改善的细胞摄取以及改善的细胞毒性和抗转移特性。另外，体内动物肿瘤模型显示与安慰剂相比具有显著的抗肿瘤功效和促肿瘤标志物的减少，且不影响裸鼠的体重和生理状态。总体而言，成功制备了表面修饰有AMD3100的载ACA的NLC，有大量抗癌功效的证据。这些结果表明AMD3100修饰的NLCs作为细胞毒性药物向表达CXCR4的癌细胞的靶向载体的潜在用途。
