Liangfang Zhang

About Liangfang's Work

Liangfang Zhang is a chemical engineer and bioengineer creating novel nanotechnologies for targeted drug delivery, medical countermeasures such as vaccines and antibacterial and antiviral drugs, and other biomedical applications. Zhang develops cell membrane coated nanoparticles that can achieve unprecedented levels of interaction with biological systems like the human body. His efforts to translate his lab research for clinical use show the potential for cellular nanoparticle (CNP) platforms to deliver active drugs to target sites or to function as therapeutics themselves while minimizing undesirable or toxic side effects.

Nanoparticles have unique physical and chemical properties that are highly desirable for medical use. However, designing synthetic nanoparticles that can both safely evade a host’s immune system and perform the intended biological interactions (such as drug delivery to a tumor site) has proved challenging. With the key insight that mimicking host cells could improve nanoparticle activity, Zhang was the first to conceive of and develop methods for coating synthetic nanoparticles with natural cell membranes. He first engineered nanoparticles cloaked with red blood cell (RBC) membranes that retain the proteins, lipids, and carbohydrates native to the RBC membrane surface. Zhang demonstrated that with this biomimetic interface, CNPs are not attacked by the immune system, enabling prolonged circulation and effective drug delivery in the body. He has also established that CNPs can target and interact with specific cell types, toxins, or pathogens via the receptors on the membrane coating. For example, he showed that CNPs coated with RBC membranes can act as universal decoys for many different toxins that attack red blood cells. By displaying the same membrane function, the RBC CNPs lure toxins away from red blood cells and bind them, thereby neutralizing them. Zhang has illustrated a range of applications using membranes derived from different cell types, such as CNPs coated with white blood cell (WBC) membranes that can neutralize cytokines and viruses that interact with receptors on WBCs, creating a versatile therapeutic platform for treating diverse inflammatory and infectious diseases; and nanodiscs made of microphage (a type of WBC) membranes that can directly bind to and disrupt antibiotic-resistant bacteria, providing a potential new treatment for antimicrobial-resistant bacterial infections.

More recently, Zhang and collaborators have explored the use of CNPs propelled by microrobots for enhanced tissue penetration and drug uptake. They demonstrated that inhaling an aerosol of platelet CNPs combined with biohybrid microalgae robots provides more homogeneous distribution and longer retention in the lungs, which improves outcomes for bacterial pneumonia. Zhang is at the forefront of advancing nanomedicine for the treatment and prevention of a range of infectious diseases, cancers, and immunological and inflammatory disorders.