Protein therapeutics form a cornerstone of modern medicine, providing effective treatments for a wide range of conditions, including cancer, autoimmune diseases, and metabolic disorders. Despite their significant success, therapeutic proteins encounter substantial biological challenges, such as enzymatic degradation, rapid renal clearance, immune activation, limited cellular uptake, and difficulties in crossing critical barriers like the blood-brain barrier. Current delivery methods, such as subcutaneous and intravenous administration, inadequately address these obstacles, underscoring the need for advanced delivery platforms.Nanotechnology has emerged as a transformative approach to overcoming these challenges. Among nanocarriers, lipid-based nanoparticles, polymeric systems, protein-based carriers, virus-like particles, inorganic nanocarriers, and antibody-drug conjugates (ADCs) have demonstrated considerable promise, with several achieving FDA approval. However, significant limitations persist, including immunogenicity, stability issues, off-target effects, and high production costs.
To address these challenges, our group has developed an innovative nanocapsule platform technology for protein therapeutic delivery. However, the potential of polymer-based protein nanocomplexes remains far from fully realized. In my dissertation, I aim to advance this field by focusing on two key objectives:
1.Development of coacervate-based protein nanocomplex for multi-enzyme cascade encapsulation and treatment for cancer starvation therapy
2.Design of virus-mimicking intracellular protein and gene delivery systems via direct cell-membrane penetration
This versatile platform represents a customizable solution to overcoming biological barriers, enhancing therapeutic efficacy, and addressing persistent challenges in protein delivery. The proposed nanocomplex systems mark a significant step forward in advancing nanomedicine, with the potential to meet critical unmet medical needs and pave the way for future innovations in therapeutic delivery.