School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China.
Int J Nanomedicine. 2020 Oct 29;15:8369-8382. doi: 10.2147/IJN.S274842. eCollection 2020.
Auraptene (AUR), a natural bioactive prenyloxy coumarin, is a highly pleiotropic molecule that can bind to the MT1 receptor and can effectively reduce the proliferation and migration of breast cancer cells. Cisplatin (CDDP), as the first synthetic platinum-based anticancer drug, is widely used in the clinic due to its definite mechanism and therapeutic effect on diverse tumors. However, both of AUR and CDDP exhibit some disadvantages when used alone, including poor solubility, low bioavailability, lack of selectivity and systemic toxicity when they are used singly.
Therefore, the biodegradable materials hyaluronic acid (HA) and β-cyclodextrin derivative (mono-(6-amino-mono-6-deoxy)-β-CD, CD) were employed as carriers to load AUR and CDDP to form nanogel (HA-CD@AUR) capable of dual-targeted delivery and synergistic therapy for breast cancer and cell imaging.
With the help of the CDDP-crosslinked CD-loaded structure, the newly synthesized nanogel exhibited excellent physiological stability and fluorescence effects. The release of AUR and CDDP was affected by the pH value, which was beneficial to the selective release in the tumor microenvironment. Cell experiments in vitro demonstrated that the nanogel could be selectively internalized by MCF-7 cells and exhibited low cytotoxicity to HK-2 cells. Antitumor experiments in vivo showed that the nanogel have better antitumor effects and lower systemic toxicity.
Based on these, the nanogel loaded with AUR and CDDP have the potential for targeted delivery against breast cancer.
白皮杉醇（AUR），一种天然生物活性的丙烯氧基香豆素，是一种具有高度多效性的分子，能够与 MT1 受体结合，有效抑制乳腺癌细胞的增殖和迁移。顺铂（CDDP）作为第一个合成的基于铂的抗癌药物，由于其明确的作用机制和对多种肿瘤的治疗效果，在临床上得到了广泛的应用。然而，AUR 和 CDDP 单独使用时都存在一些缺点，包括溶解度差、生物利用度低、缺乏选择性以及全身毒性。
因此，采用可生物降解材料透明质酸（HA）和 β-环糊精衍生物（单（6-氨基-单-6-去氧）-β-CD，CD）作为载体，将 AUR 和 CDDP 负载形成能够双重靶向递送和协同治疗乳腺癌和细胞成像的纳米凝胶（HA-CD@AUR）。
在 CDDP 交联的 CD 负载结构的帮助下，新合成的纳米凝胶表现出优异的生理稳定性和荧光效果。AUR 和 CDDP 的释放受到 pH 值的影响，有利于在肿瘤微环境中进行选择性释放。体外细胞实验表明，纳米凝胶可以被 MCF-7 细胞选择性内化，对 HK-2 细胞的细胞毒性较低。体内抗肿瘤实验表明，纳米凝胶具有更好的抗肿瘤效果和更低的全身毒性。
基于这些，负载 AUR 和 CDDP 的纳米凝胶具有针对乳腺癌的靶向递送潜力。
