Zhang Tao, Li Xiao, Wu Liang, Su Yue, Yang Jiapei, Zhu Xinyuan, Li Guolin
Key Laboratory of Microecology-immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi, China.
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Bioeng Biotechnol. 2024 Feb 13;12:1364975. doi: 10.3389/fbioe.2024.1364975. eCollection 2024.
Cisplatin (CDDP) is widely used as one kind of chemotherapy drugs in cancer treatment. It functions by interacting with DNA, leading to the DNA damage and subsequent cellular apoptosis. However, the presence of intracellular PARP1 diminishes the anticancer efficacy of CDDP by repairing DNA strands. Olaparib (OLA), a PARP inhibitor, enhances the accumulation of DNA damage by inhibiting its repair. Therefore, the combination of these two drugs enhances the sensitivity of CDDP chemotherapy, leading to improved therapeutic outcomes. Nevertheless, both drugs suffer from poor water solubility and limited tumor targeting capabilities. To address this challenge, we proposed the self-assembly of two drugs, CDDP and OLA, through hydrogen bonding to form stable and uniform nanoparticles. Self-assembled nanoparticles efficiently target tumor cells and selectively release CDDP and OLA within the acidic tumor microenvironment, capitalizing on their respective mechanisms of action for improved anticancer therapy. studies demonstrated that the CDDP-OLA NPs are significantly more effective than CDDP/OLA mixture and CDDP at penetrating cancer cells and suppressing their growth. studies revealed that the nanoparticles specifically accumulated at the tumor site and enhanced the therapeutic efficacy without obvious adverse effects. This approach holds great potential for enhancing the drugs' water solubility, tumor targeting, bioavailability, and synergistic anticancer effects while minimizing its toxic side effects.
顺铂（CDDP）作为一种化疗药物在癌症治疗中被广泛使用。它通过与DNA相互作用发挥作用，导致DNA损伤并随后引发细胞凋亡。然而，细胞内PARP1的存在通过修复DNA链降低了CDDP的抗癌效果。奥拉帕利（OLA），一种PARP抑制剂，通过抑制DNA修复增强了DNA损伤的积累。因此，这两种药物的联合使用增强了CDDP化疗的敏感性，从而改善了治疗效果。然而，这两种药物都存在水溶性差和肿瘤靶向能力有限的问题。为了应对这一挑战，我们提出通过氢键作用使CDDP和OLA这两种药物自组装形成稳定且均匀的纳米颗粒。自组装纳米颗粒能够有效地靶向肿瘤细胞，并在酸性肿瘤微环境中选择性地释放CDDP和OLA，利用它们各自的作用机制来改善抗癌治疗。研究表明，CDDP - OLA纳米颗粒在穿透癌细胞和抑制其生长方面比CDDP/OLA混合物和CDDP显著更有效。研究还表明，纳米颗粒特异性地在肿瘤部位积累，增强了治疗效果且无明显不良反应。这种方法在提高药物的水溶性、肿瘤靶向性、生物利用度以及协同抗癌效果的同时，将其毒副作用降至最低，具有巨大的潜力。
