Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing 400030, China.
Department of Oncology, Chongqing People's Hospital, Chongqing 401147, China.
Biomater Sci. 2022 Aug 24;10(17):4837-4847. doi: 10.1039/d2bm00603k.
Nanomedicines represent new promising strategies for treating atherosclerosis (AS), because they enhance drug bioavailability and have lower side effects. Nevertheless, nanomedicines have several challenges with these advantages, including a limited circulation life, lack of precise targeting, and insufficient control of drug release. Accordingly, the development of drug delivery systems (DDSs) with abilities to enhance the payload delivery to the AS plaque lesion and to control drug release can boost the therapeutic efficacy and safety for AS treatment. Herein, we employed a one-step self-assembly approach for effectively encapsulating the anti-AS drug simvastatin (SIM) in zeolitic imidazolate framework-8 (ZIF-8) (SIM/ZIF-8), and then coated it with hyaluronic acid (HA) to fabricate the SIM/ZIF-8@HA nanoplatform. The resulting nanoplatform could efficiently accumulate in plaque regions through the specific recognition between HA and CD44. Meanwhile, the acid environment breaks down ZIF-8 to release SIM. The and experiments demonstrated that SIM/ZIF-8@HA could inhibit the proliferation of smooth muscle cells and have good biocompatibility. Moreover, SIM/ZIF-8@HA can effectively suppress the development of AS plaques without any considerable side effects in mice treatments. The findings revealed that SIM/ZIF-8@HA may be a promising nanomedicine for safe and efficient anti-AS applications.
纳米医药为治疗动脉粥样硬化（AS）提供了新的有前途的策略，因为它们可以提高药物的生物利用度，降低副作用。然而，纳米医药在具有这些优势的同时也面临着一些挑战，包括循环寿命有限、缺乏精确靶向和药物释放控制不足等问题。因此，开发具有增强药物递送至 AS 斑块病变的能力并控制药物释放的药物传递系统（DDS）可以提高 AS 治疗的疗效和安全性。在此，我们采用了一步自组装的方法，有效地将抗 AS 药物辛伐他汀（SIM）封装在沸石咪唑骨架-8（ZIF-8）中（SIM/ZIF-8），然后用透明质酸（HA）对其进行涂层，制备了 SIM/ZIF-8@HA 纳米平台。所得纳米平台可以通过 HA 与 CD44 之间的特异性识别，有效地在斑块区域聚集。同时，酸性环境会破坏 ZIF-8 以释放 SIM。和 实验表明，SIM/ZIF-8@HA 可以抑制平滑肌细胞的增殖，具有良好的生物相容性。此外，SIM/ZIF-8@HA 可以有效地抑制 AS 斑块的发展，而在小鼠治疗中没有任何明显的副作用。研究结果表明，SIM/ZIF-8@HA 可能是一种安全有效的抗 AS 应用的有前途的纳米药物。
