[Abstract]

Nanoparticles (NPs) are widely explored as drug carriers in order to alter the pharmacokinetics and biodistribution of their drug payloads, thereby enhancing their efficacy and reduce side effects. For example, NPs are excellent tools for the treatment of intracellular bacterial infection due to the ability to enter cells that the commonly used antibiotics cannot easily access. With optimal size and composition, NPs can bring a large amount of antibiotics into the infected cells with little effects on normal tissues. Our lab has developed NP system that can deliver vancomycin to methicillin-resistant staphylococcus aureus (MRSA)-infected macrophages and effectively reduce the bacterial burden in the cells. NPs have also been explored for targeted delivery of chemotherapeutic drugs to tumors based on hyperpermeability of tumor vasculature that allows selective access of NPs. This promise has recently been challenged as leading NP products did not meet expectations in clinical trials. We recognize several obstacles that current NP technologies have not properly overcome, such as poor circulation stability, limited drug loading capacity of NPs, and immunosuppressive microenvironment of tumors. Our lab has developed new strategies to enhance the delivery of NPs to tumors. Such efforts include the development of (i) quinic acid-coated polymeric nanoparticles, which interact with peritumoral endothelium for efficient extravasation in tumors, (ii) albumin-coated nanocrystals, which exploit the albumin-transport mechanism to reach tumors, and (iii) tannic acid-self-assembled nanocapsules, which deliver immunogenic cell death inducers to modulate tumor immunoenvironment. In this talk, I will introduce our new NP drug delivery systems and discuss remaining challenges and opportunities.