pH-Responsive hyaluronic acid-enveloped ZIF-8 nanoparticles for anti-atherosclerosis therapy

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 in vitro and in vivo 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.