Biomimetic Nanodelivery

The development of nanoparticles that carry drugs to target sites in the body promises safer and more effective drug delivery. Surface modification of drug nanocarriers to enhance their compatibility with the body and to improve drugs’ ability to target desired cells and tissues is of critical importance, but remains an unmet challenge. By turning to nature for design cues, we created an innovative biomimetic nanoparticle platform via cloaking synthetic nanoparticles with cellular membranes extracted directly from natural cells. As one example, upon red blood cell (RBC) membrane coating, the nanoparticles are equipped with the complex immunomodulatory proteins that are naturally found in the RBC ’s external membrane. These nanoparticles can thus evade the body’s immune system for extended periods of time, continuing to circulate unnoticed through the bloodstream, effectively delivering their drug payload. As another example, by coating nanoparticles in the plasma membrane of platelets, the nanoparticles display platelet-mimicking properties such as selective adhesion to damaged vasculatures and enhanced binding to platelet-adhering pathogens for targeted drug delivery. This cell membrane coating technology opens a whole new set of opportunities for the nanotechnology and nanomedicine communities.

Countermeasure Nanotherapeutics

Chemical and biological toxicants from wound infections, venomous injuries, and biochemical weaponry impose significant threats on public health. Many different types of toxins have been identified, displaying diverse molecular structures and distinctive epitopic targets. Despite of these differences, the functional similarity among these toxins in interacting with cellular membranes provides the design cue for an action mechanism-targeted detoxification platform with a broad applicability. We invented an entirely new toxin "nanosponge" platform that targets the membrane-interacting toxicants and functions as a universal toxin decoy to absorb and remove effectively different types of toxins regardless of their molecular structures. As one example, we utilize such toxin nanosponges to neutralize a wide range of pore-forming toxins secreted by pathogenic bacteria such as Staphylococcus aureus. By removing the virulence factors from the bacteria (i.e., "disarming" the bacteria), the nanosponges enable the immune cells to take over the powerless pathogens; thereby no antibiotics are involved in the treatment of bacterial infection. As another example, we utilize the nanosponges as a countermeasure of organophosphorus compounds and other nerve agents. By scavenging these toxic molecules, the nanosponges provide an effective, broad-spectrum treatment of chemical agent poisoning.

Vaccine Nanotechnology

To improve innate defense against diseases, vaccines are routinely applied to mount immune responses against disease-causing cells or organisms. These vaccine formulations are typically prepared with weakened forms of cells/ microbes, their surface proteins, or their virulence factors, which can train the immune system to recognize and neutralize similar biological threats in later exposures. Owing to many unique properties of nanoparticles in enhancing vaccine potency, nanoscale carriers are drawing increasing interest for developing safer and more effective vaccine formulations. We recently made some exciting contributions to the field of vaccine nanotechnology. As one example, we demonstrate a nanoparticle-based detainment strategy, by sequestering intact membrane-active toxins within a nanoparticle, to safely deliver non-denatured protein toxins to mount a safe and potent anti-toxin immune response against bacterial infection. As another example, we develop a robust cancer vaccine employing an entirely new cancer cell membrane-coated nanoparticle. By synthesizing adjuvant-loaded polymeric nanoparticles and coating them with autologous tumor cell-derived plasma membrane, we create a personalized cancer vaccine capable of training the immune system against multiple tumor antigens without the need for tumor antigen identification.