Our research interests lie at the interface of chemistry and biology with particular emphasis on nanocarrier mediated delivery of metal-based drugs for their potential applications in various diseases and in the development of nano-vaccines. We are focused on interdisciplinary approaches for drug development. Our lab strategically place research at the interface of biological chemistry and nanotechnology. Despite the progress made in using nanocarriers in cancer therapy to increase tissue accumulation of drug molecules to improve efficacy and to reduce unwanted side effects, successful sub-cellular targeting of drugs specifically to cell organelles has only recently gained broader recognition. Many drugs have target sites inside the cell, at specific cell organelles or even inside organelles such as mitochondria. Our research is directed to develop organelle targeting polymeric nanoparticle-metal complex constructs, and to study nanoparticle assisted targeted delivery and the anticancer properties. Our lab develops technologies that use a combination of conventional methods of cancer treatment and immunotherapy in a single nanoparticle platform to provide powerful low-cost tool to treat cancer in humans.

We work in the areas of diagnosis and combination therapies for cancer and cardiovascular disease with particular emphasis on nanomedicine for solid tumors that are highly metastatic. Our research program includes pre-clinical and clinical testing of different nanomedicine platforms. As a research team with a strong background in chemistry, we aim to provide the scientific community with valuable knowledge that can guide into the discovery of potential drug candidates and vaccines.

Our lab strategically places research at the interface of biological chemistry and nanotechnology. Currently we are working in the following research areas:

Project 1: Despite the progress made in using nanocarriers in cancer therapy to increase tissue accumulation of drugs to improve efficacy and to reduce side effects, successful sub-cellular targeting specifically to organelles has only recently gained broader recognition. Until now, little effort has been focused to deliver organelle-targeting drugs selectively to a sub-cellular compartment of the cancer cells. Our research is directed to develop organelle targeted engineered nanoparticles that will offer several advantages over the existing drugs

Project 2: Our lab develops technologies that use a combination of conventional cancer treatment and immunotherapy in a single nanoparticle platform to provide powerful tool to treat metastatic cancer.

Project 3: We are working to test a combined approach for diagnosing and treating pancreatic cancer with a specially engineered nanoparticles.

Project 4: Our research program is also focused to develop nano-sensors for apoptosis detection in atherosclerotic plaques. The overall objective of our project is to develop and apply a targeted long-circulating magnetic resonance imaging (MRI) active nanoparticle platform that selectively targets macrophages inside atherosclerotic plaques and can sense apoptosis.

Subgroups:

Immune System Boosted Combination Therapy: Cancer that spreads to other organs or to lymph nodes far from the primary tumor is called metastatic disease. Despite early diagnosis and treatment, cure is not possible for most patients with metastatic breast, pancreatic, prostate, and skin cancers. The effective method is to use our immune system to recognize cancer cells as foreign body and remove the metastatic tumor. In the setting of metastatic cancer, combination therapy is preferable. Therapeutic challenges when administering drug combinations include the choice of dosages to reduce side effects, the definitive delivery of the correct drug ratio, and exposure to the targets of interest. These factors are very difficult to achieve when drugs are individually administered. By combining controlled release nanoparticle drug delivery approaches, we aim to differentially deliver conventional drugs along with synergistic immune-stimulators to manage the distant tumors in a temporally regulated manner resulting in safer and more effective management of metastatic cancers.

Members of the Sub-group:
Sean Marrache

Joshua Choi

Dhillon Zaver

Cardiovascular Imaging and Therapy: Atherothrombotic vascular disease (ATVD) is responsible for more deaths than any other disease in the industrialized world. To detect atherosclerotic evidence noninvasively, we are working in constructing long-circulating nanoparticle platform, which can selectively target macrophages and sense apoptosis in cardiovascular diseases.

Members of the Sub-group:

Sean Marrache: Sean is working on constructing HDL cholesterol based nanoparticles for atherosclerosis. HDL cholesterol or Good cholesterol helps remove the Bad LDL Cholesterol from arteries. He is constructing HDL-based nanoparticles as a carrier to deliver diagnostic iron oxides and statin therapy for the management of cardiovascular diseases.

Rakesh Pathak will also work on multifunctional nanoparticles for imaging and therapy of ATVD. His work involves constructing hybrid nanoparticle systems by encapsulating MRI active iron oxide nanocrystals in a polymeric matrix. The NP surface is further modified by macrophage targeting ligands, PS-targeting peptides, and Zn2+ binding domains, which can bind the apoptotic macrophages with a real potential for clinical diagnoses.

Dhillon Zaver is working with Rakesh on apoptosis sensing project.

Akil Kalathil is working on detection of vulnerable plaques

Organelle-Targeted Delivery: The success of any therapy is directly related to the treatments ability to reach the target of interest. Targeted therapy is a rapidly growing approach for the treatment of various diseases. Nanotechnology-based differential combination therapy can be emphasized as a promising therapeutic strategy. The cytoplasm, nucleus, and mitochondria have been considered as primary targets for drug delivery using targeting moieties or environment-responsive materials. We are developing organelle-targeted carriers specialized to target the cytoplasm, nucleus, mitochondria, and other organelles for combination therapy of various diseases including but not limited to cancer, obesity, and Alzheimer's Disease.

Members of the Sub-group:
Sean Marrache: Sean is currently working on engineering targeted drug delivery systems to direct therapeutics to the mitochondria of the target cells, allowing an effective action for the disease of interest. This design would result in a higher local concentration of the active species involved in the mitochondria of target cells. In order to study this hypothesis, Sean has initiated the synthesis of a series of mitochondria targeting polymers to study nanoparticle assisted targeted delivery mitochondria targeting therapeutics to their target cells.

Andrew Cooper: Andrew is working on a nanoparticle platform based on biocompatible and/or biodegradable polymers with increased number of targeting moieties, an increased ligand density may increase target binding, making the nanoparticle target specific. He is synthesizing dendrimer end functionalized biodegradable polymers which will lead to a controlled incremental increase in the surface groups in the nanoparticles for efficient targeting.

Kasey Darley: Kasey is working on mitochondria-targeted delivery of therapeutics.

Malikah Christie is working on mitochondria-targeted delivery of therapeutics.

Nanotheranostics: The overall goal of this subgroup is to develop and apply a long-circulating theranostic nanoparticle platform that effectively targets pancreatic cancer cells by a combination therapeutic approach. Theranostics allows diagnostic therapy and we apply magnetic resonance imaging (MRI) to visualize nanoparticle accumulation that locally and gradually releases anti-cancer therapy. Our work involves synthesis of NP platform, to show its efficacy in vitro, and to ultimately demonstrate its potential for pancreatic cancer in vivo.

Our work involves synthesis of NP platform, to show its efficacy in vitro, and to ultimately demonstrate its potential for pancreatic cancer in vivo.

Members of the Sub-group:
Yasir Bouchi: Yasir is working to create a nanoparticle drug-delivery system that will allow diagnosis and treatment of pancreatic cancer. He is using iron oxide nanoparticles to visualize uptake via MRI. A photocleavable linker conjugated to a photosensitizing agent and a chemotherapeutic will allow simultaneous delivery of treatment via photodynamic therapy (PDT) and chemotherapy.