We are interested in developing next generation biomaterials for drug delivery and tissue engineering. Our focus is on synthesizing libraries of materials that have varying chemical and structural properties. Some of the parameters that we are most interested in controlling are drug cargo binding properties, rate and mechanism of degradation, biocompatibility, and cell/material interactions. It is important that our materials are designed to be non-cytotoxic, non-immunogenic, and either biodegradable or bioeliminable. We use these biomaterials to construct our particles, coatings, and devices.
We are developing multi-functional nanoparticles for varied applications. Drug, imaging, or biosensor cargos are electrostatically bound, adsorbed to the surface, or physically encapsulated within our nanoparticles. Another aspect of our research is developing multilayered coatings to improve functionality of particles or devices. We utilize our biomaterial libraries to find the best material to shuttle the desired cargo to the target cells in a controlled manner. One class of cargos that we are interested in is nucleic acids to enable the delivery of genetic medicine. DNA and RNA can be delivered to turn on or off genes individually or in combination. We are interested in multiple strategies for RNA therapeutics including silencing on the translational level as well as silencing or activating at the transcriptional level. The delivery of plasmid DNA enables transcriptional control of expression of key genes or shRNA silencing sequences. As more information is gleaned from the human genome, additional targets for genetic medicine are found. The central challenge to developing genetic medicine is a safe and effective method for delivery. We aim to develop nanobiotechnology that can efficiently and safely target particular tissues and cells extracellularly and particular organelles intracellularly to meet this challenge.
We are designing next generation materials that have biomimetic properties and interface with the immune system. In some cases these materials activate the immune system to mount an attack against metastatic cancer cells. In other research, we are suppressing the immune system locally for tissue engineering and transplantation. In designing particles to be biomimetic, we are especially interested in the role of shape in mediating cellular interactions. For example, we have found that “football” -shaped particles that function as artificial antigen presenting cells lead to stronger immune activation of cytotoxic T cells than similarly constructed spherical particles.
Rational Design for Controlled Drug and Gene Delivery
Developing effective drug and gene therapies remains a challenge because there are many barriers to efficient delivery. The steps are complex and include encapsulation and protection of the cargo molecule(s), cell specific internalization, particle trafficking through the cell, escape from the endosomal compartment into the cytoplasm, and controlled cargo release. For certain cargos, there are additional downstream barriers including transport to a target organelle, and in the case of DNA, efficient transcription and translation. We are developing high-throughput, quantitative assays that will enable us to more precisely measure how varying biomaterial structural properties and particle biophysical properties affect delivery at each of these steps. By quantifying these bottlenecks and developing material and cell-specific parameters, we aim to create a computational model to describe delivery. Through in silico modeling we aim for rational design of advanced biomaterials.
Targeted Cancer Therapeutics
In the Green Group, we are motivated by the potential of our research to lead to improvements in human health. At Hopkins, we seek out collaborations where we can combine our technologies with a clinical need to make this difference. One of the areas where there is a great need for improved therapeutics is cancer. One and a half million Americans develop cancer each year and over 550,000 Americans tragically die from it annually. Nanobiotechnology can improve cancer therapy by enabling smarter targeting of the cancer and reduced off-target side effects in healthy cells. There are many levels where the therapeutic safety/efficacy window can be improved including: passive targeting of nanoparticles to the leaky vasculature of the tumor, tumor-specific internalization of the nanoparticles, tumor-specific drug cargo release, and cargos that are preferentially active in the cancer as compared to healthy cells. For the case of gene delivery, there is additionally transcriptional targeting, so that even if there is some off-target nanoparticle delivery, the therapeutic genes will be selectively expressed in the cancer cells of interest. Of particular interest to us is the targeting of cancer stem cells.
Stem Cells and Regenerative Medicine
Regenerative medicine holds the promise of treating myriad diseases through cellular therapies and the potential replacement of tissues. As one of the Cell and Tissue Engineering research labs in Biomedical Engineering, we are very interested in regenerative medicine. One of the key difficulties in cell and tissue engineering is controlling cell differentiation. We utilize our biomaterials and nanobiotechnology toolkit to better control cell state and function. We are particularly interested in non-viral methods to differentiate stem cells to desired lineages as well as control expression of key factors to reprogram differentiated cells into less differentiated, stem cell-like states.