Author + information
- Ma Qian,
- Jiefang Sun and
- Yujie Zhou
Cardiovascular disease is the leading cause of death in the world. The most manifest contributor to cardiovascular morbidity and mortality is atherosclerosis. When atherosclerotic plaques rupture, it can cause clinical events such as myocardial infarction and stroke. The plaques prone to rupture are described as ‘vulnerable plaques'. Statins can reduce the inflammation of atherosclerosis in high-dose therapy, however, inducing potential risks (e.g. liver dysfunction, rhabdomyolysis). Meanwhile, statins present with low bioavailability if orally taken. Nanotechnology provide a new approach to stable vulnerable plaques. Nanoparticles can provide a variety of delivery systems which can increase drug concentrations in targeted tissues, improve the efficiency of drugs, decrease the required dosage, reduce the side-effects of oral administration. Our objective is to produce new-style nanoparticles which can detect, stabilize and reversal vulnerable plaques.
The project attempts, with CD44 in vulnerable plaques targeted, to construct nanoparticle with cerasome as carriers, SPIONs/rosuvastatin loaded in the interior lumen, and hyaluronic acid (HA) as targeting molecules. These nanoparticles are thus intended to actively target and accumulate inside of vulnerable plaques, releasing drugs to stabilize and reversal vulnerable plaques. Assess the safety, targeting efficiency and intake capability of the HA- SPIONs/rosuvastatin-nanoparticles via in-vitro tests. Establish the ApoE -/- mice model of vulnerable atherosclerotic plaques to evaluate the detection and efficacy of HA-SPIONs/Rosuvastatin- nanoparticles.
We demonstrate the HA-SPIONs/Rosuvastatin-nanoparticles are consumed by macrophages in vitro. And it is shown that HA-Rosuvastatin- nanoparticles has anti-inflammatory effect in vitro. We also apply HA-SPIONs-nanoparticles in vivo in apolipoprotein E-knockout mice model of vulnerable plaques and Magnetic Resonance Imaging (MRI) shows that they generated a stronger signal by accumulating at the inside of vulnerable plaques. Meanwhile, we demonstrate that a 10 days HA-rosuvastatin-nanoparticles treatment regimen inhibits plaque inflammation progression and reversals vulnerable plaques.
This study purposes itself, through a cross-study of multi-fields and multi-subjects, as in the intertwinement of basic and clinical medicine, as well as chemistry and medicine, to achieve a breakthrough in the targeted detection and therapy of vulnerable plaques. This study shows that vulnerable plaques are successfully detected by HA-SPIONs/Rosuvastatin-nanoparticles and animal study showed positive effects of enhancing therapeutic efficacy. The new-style nanoparticles providing new insights in the reduction of the morbidity and mortality rates of cardiovascular diseases.