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 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 nanotechnology opens a whole new set of opportunities for nanomedicine and bioengineering research.

Chemical and biological threat agents including numerous toxicants and emerging viruses impose significant threats on public health. Many different types of toxins and viruses have been identified, displaying diverse molecular structures and distinctive epitopic targets. Despite of these differences, the functional similarity among these threat agents in interacting with host cell membranes provides the design cue for an action mechanism-targeted detoxification platform with a broad applicability. We invented an entirely new "cellular nanosponge" platform that targets the membrane-interacting toxicants or viruses and functions as a universal nanodecoy to capture and neutralize different types of threat agents. As one example, we utilize cellular nanosponges to neutralize a wide range of bacterial toxins. By removing the virulence factors from the bacteria ("disarming" the bacteria), the nanosponges enable the immune system to take over the powerless pathogens. As another example, we employ cell-mimicking nanosponges to bind with various species or families of viruses, including SARS-CoV-2, blocking their cellular entry and inhibiting viral infectivity. In this research area, we are actively developing novel anti-viral, anti-toxin, and anti-inflammation therapies.

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 agents 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 vaccines. We are particularly interested in developing nanovaccines and studying their interactions with the immune system. 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. As another example, we develop a robust cancer vaccine employing an entirely new cancer cell membrane-coated nanoparticle. By synthesizing adjuvant-loaded 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.