Nano-immunotherapy

研究论文

书籍章节

发明专利

Research

The goal of the nano-immunotherapy is to take full advantage of nanotechnology to provide new opportunities and strategies for settling problems raised in immunotherapy. It mainly focuses on the development of diverse nano-vehicles for persistent, controllable and targeted delivery of antigens or therapeutic agents to interested cell populations. Besides the most widely used nano-immunotherapeutic approaches for cancer treatments which manipulate host immune system to target and destroy cancer cells, our laboratory currently pays a close attention to the nano-immunotherapy for infectious diseases (e.g., infected macrophages). Infectious diseases are associated with high morbidity and mortality worldwide. They can be treated with antibiotics, however, the low bioavailability of antibiotics limit their therapeutic performances. Moreover, antibiotic therapy shows many side effects, long treatment periods, difficulty in killing intracellular bacteria, and bacterial resistance to antibiotics. With the emergence of resistant strains (e.g., super bacteria), the treatment of infectious diseases has become more challenging. Delivering antibiotics by nanoparticles will improve drug bioavailability and enhance intracellular bacterium eradication. We developed a nanogel responsive to special local environment generated by the infecting bacteria to deliver anti-infectious drugs, improving the selective uptake of drugs by infection-associated immune cells (e.g., macrophages) and promoting anti-infection efficacy of treatment while reducing the side effects.

A general method of preparation was adopted to prepare nuclear cross-linked polyphosphate nanogel through the arm-first and one step ring-opening polymerization. The nanogel consisted of polyethylene glycol as the shell and polyphosphate cross-linked as the core which can be degraded by phospholipase, with enzyme-responsive drug release properties (Macromolecules, 2009, 42, 893-896).

1. Through the strategy described above, we developed mannosylated multifunctional polyphosphate nuclear cross-linked nanogels. It turned out that they were able to enhance the uptake of entrapped antibiotics by macrophages, followed by their transport at the site of bacterial infection, leading to antibiotic accumulation locally and bacterial drug release by bacterium-engulfing macrophages. Using the zebrafish embryos infection model, mannose mashing nanogels showed macrophage-targeting capabilities and responsive release of antibiotics in the infected area of MW2, improving drug delivery efficacy (Advanced Materials, 2012, 24, 6175-6180).

2. Based on the previous work, we further developed a nanogel that can selectively deliver antibiotics to bacterial infection sites. The nanogels have a three-layer structure, composed of polyethylene glycol shell cross-linked with poly phosphate as the core and polycaprolactone (PCL) as an intermediate; the PCL sandwich was sensitive to the lipase secreted by bacteria. In aqueous medium, PCL formed a layer of dense hydrophobic molecule wall to prevent the drug release before nanoparticles reach to infection sites; when nanogels sensed lipase secreted by bacteria, PCL molecule wall was degraded by lipase, resulting in the rapid release of the drug, which effectively kills the bacteria (J Am Chem Soc, 2012, 134, 4355-4362).