Figure 1. Based on the complimentary characteristics of synthetic polymers and biopolymers, two approaches will be undertaken in our group to generate A) hybrid materials composed of the two types of macromolecules in a synergistic manner; and B) bio-inspired synthetic materials that possess biologics-like properties and functions. These materials will find numerous applications in biomedical researches and we are particularly interested in applying them for cancer immunotherapy and RNA-targeting therapy.
Biological macromolecules, such as DNA and protein, are the products of billions of years of natural evolution. They are distinguished from synthetic polymers by their defined primary sequences and near-perfect homogeneity (if we do not consider epigenetic modifications), which form the physical basis for a wide scope of life-defining biochemical mechanisms, ranging from the storage of genetic information and encoding of protein sequences, to molecular recognition and interaction. To this end, one ultimate goal of polymer science is to create synthetic macromolecules that can rival their natural counterparts from the perspectives of structural homogeneity and functional complexity. Recent advances in controlled polymerization technologies and functional polymeric materials have been inspiring growing research endeavor in simulating the capabilities of biological macromolecules in the past decades.
At the Lu Lab, we are dedicated to bridging the worlds of biological and synthetic macromolecules using an integrated approach encompassing cutting-edge technologies in synthetic polymer/organic chemistry, molecular biology, immunology and biomedicine. We hope to apply our arsenal of scientific knowledge and tools to the understanding of fundamental principles that govern the synthesis and functions of biological macromolecules and to the development of novel materials that can fulfill a diversity of engineering and medical needs.
Specifically, our research interests span the following domains:
A) Developing new technologies to conveniently synthesize site-specific and structurally well-defined hybrid materials composed of biological macromolecules and synthetic polymers (Fig.1A).
Exemplified by protein pegylation, hybrid materials synergistically integrating both synthetic and biological macromolecules may offer improved physicochemical properties and enhanced bio-functions. However, it remains a fundamental challenge to facilely synthesize site-specific and structurally well-defined hybrid materials under mild and biological-relevant conditions. We are interested in 1) developing more efficient and effective synthetic technologies, and 2) creating a group of new hybrid materials with reversible, responsive and enhanced biological functions by sophisticated molecular design and the introduced synthetic polymers in the hybrids.
B) Generating synthetic materials via bio-inspired approaches to precisely modulate and mimic the complex pathways and functions of biological macromolecules (Fig.1B).
As polymer chemists, we are always fascinated about the degree of delicacy, fidelity, and complexity that the biologics can accomplish and it is always wise to learn from the nature. One goal of our researches is to develop biomimetic approaches and synthesize high molecular-weight polymers with absolute monodispersity and defined sequences in a rapid, low-cost and scalable manner. Moreover, we are thrilled to generate artificial materials that can simulate and replace the functions of biological polymers to some extent (e.g. artificial antibodies and enzymes, synthetic polypeptides polymers, and nucleic acids with new genetic alphabets).
C) Developing materials and platforms for biomedical applications (Fig.1C).
The materials generated in section A) and B) will be utilized for a number of biomedical applications. One major domain of our research in biomedicine is to develop antibody conjugates or related drug candidates for cancer immunomodulation therapy, with particular emphasis on re-educating and reshaping tumor microenvironment (TME), immune activation, and vaccine development. Another exciting area we are delighted to step in is RNA-targeting therapy. RNA is at the spotlight position of the “Central Dogma” of molecular biology. The crosstalk and competition of various RNA-targeting mechanisms including the well-documented RNA interference (RNAi) and microRNA (miRNA), the newly discovered competing endogenous RNA (ceRNA) and circular RNA (circRNA) underscore the multilayered complexity of post-transcriptional regulation and its implication in disease treatment. But delivery of such large, vulnerable, and negative-charged biological macromolecules to the right organ and cellular compartment is a real hurdle of harnessing the powerful endogenous gene regulation mechanisms for therapeutic purposes. By working on both RNA-mimicking therapeutics and efficient deliver platforms, our goal is to develop next generation RNA-targeting drugs.
