Cardiovascular diseases (CVDs) remain the leading cause of mortality globally, underscoring the necessity to innovate novel strategies. Nanotechnology has emerged as a transformative strategy for targeted drug delivery via rational design. Yet, challenges persist in achieving extrahepatic targeting, such as ischemic myocardium and lesional plaques. To address these, this thesis of Han Gao focuses on developing β-glucan-based nanosystems to achieve precise drug delivery towards the conditioning of myocardial ischemic injury/atherosclerosis.
In line with the specific needs of the disease, four versatile platforms were designed and fabricated. With systematic exploration, these β-glucan-based nanosystems demonstrated selective affinity towards lesional macrophages, driven by interactions with the Dectin-1 receptor. Major pharmaceutical findings, including cost-effective synthesis method, high-throughput formulation screening, enhanced endosomal escape capability, directed delivery of genetic molecules and advanced heart-oriented treatments.
Functional evaluations were conducted using clinical-relevant murine models, revealing that these nanosystems could mitigate ischemia-reperfusion injury and inflammatory responses. Moreover, a theranostic platform integrating metal-organic frameworks (MOFs) was generated and showcased multifunctionality for simultaneous therapeutic and diagnostic applications in atherosclerosis.
In summary, this thesis integrates pharmaceutical science and biomedical engineering, advances the understanding of nanoparticles design and optimization process, promotes the development of precision medicine in CVDs. Furthermore, these findings highlight the translational potential of polysaccharide-based nanocarriers in functional drug delivery, offering valuable insights for advancing future research in this field.
