Nanotechnology has been extensively exploited to enhance the pharmacokinetic properties and therapeutic index of a variety of drugs. In the past two decades, a large number of nanoparticle-based therapeutic and diagnostic products have entered clinical development or been approved for clinical use. Liposomes and polymeric nanoparticles represent two dominant classes of nanocarriers capable of efficiently encapsulating and delivering a myriad of drug classes. Given the clinical success of liposomes and polymeric nanoparticles, we hypothesized that a lipid-polymer hybrid nanoparticle may be developed that combines the merits of liposomes and polymeric nanoparticles. The hybrid nanoparticles can be a robust drug delivery platform with high drug encapsulation yield, tunable and sustained drug release profile, excellent serum stability, long circulation half-life, and potential for differential targeting of cells or tissues. In addition, the hybrid nanoparticles are prepared through a simple synthesis process in a reproducible and predictable manner.

A serious problem with conventional chemotherapy is its inability to effectively combine drugs whose different activities interfere with multiple cellular processes and thus synergistically suppress the drug resistance of signaled cells. At present stage, the efficacy of combination drug therapy is severely limited by the fact that one can not effectively control the molar ratio of different drugs taken up by the same diseased cells, simply because each drug has different biodistribution. One strategy to overcome this problem is to load multiple drugs in a desired proportion onto a nanocarrier, and then deliver the nanocarrier to the cell of interest. After cellular internalization, the nanocarrier releases its payloads to signal multiple cellular processes. We are developing a group of lipid-based drug delivery systems that can simultaneously deliver multiple drugs with different hydrophobicity and other characteristics to the same cancer cells in a targeted manner.

Antimicrobial drugs have been prescribed intensively to kill or inhibit the growth of microbes such as bacteria, fungi and viruses. Even though the therapeutic efficacy of these drugs has been well established, inefficient delivery can result in inadequate therapeutic index and local and systemic side effects. Especially, many intracellular infections remain difficult to treat simply because of the poor cellular transport properties of antimicrobial drugs. In addition, the toxicity to healthy tissues and the acquired antimicrobial resistance of microbes also pose significant limitations to the use of antimicrobials. Nanostructured biomaterials, nanoparticles in particular, have unique biophysicochemical properties that can be applied to facilitate the administration of antimicrobials, thereby overcoming some of the aforementioned limitations. We are interested in screening for novel innate antimicrobials and developing appropriate strategies to deliver them to the target infectious microbes, with a specific focus on Propionibacterium acnes and Staphylococcus aureus bacteria, which are associated with acne infections and staph infections, respectively.

Many factors can influence nanoparticle drug delivery capability, including particle composition, size, surface chemistry and surface charge density. Presently, experimental design in the field of nanomedicine is dominated by methodologies to screen a large candidate library to pick out the desired formulation and optimal parameters. While this method has generated many successes in the past, large-pool screening usually requires tremendous cost and gives limited contribution to basic knowledge for education purpose. Thus for both practical and fundamental reasons, it is not only necessary but also urgent to understand the fundamental principles that underlie the successful development of nanomedicine. Our interests in this large area focus around understanding how single nanoparticles with distinct characteristics interact with biomembranes, with special focus on understanding cellular endocytosis and endosome escape of therapeutic nanoparticles.