Nanotechnology and Drug Delivery

Nanotechnology and Drug Delivery basic research focuses on designing new drugs that cross multiple biological barriers to block gliomas growth.

Immunotherapy is one of the fastest developing approaches in clinical oncology and has provided successful treatment of different cancers. However, the unique immune environment of the central nervous system needs consideration when pursuing immunotherapeutic approaches for gliomas. Treatment options are limited, in part, due to inefficient drug delivery across the blood-brain barrier (BBB). Therefore, new nano immunoconjugates based on natural biopolymer scaffold, poly(b-L-malic acid), with covalently attached a-CTLA-4 and/or a-PD-1 for delivery across the BBB and activation of local brain anti-tumor immune response, were developed.

Noninvasive imaging agents to precisely diagnose different brain pathological conditions are under constant development for selective targeting and treatment of brain metastasis from primary tumors originating in the lung, breast and other organs.

The aim of the Nanotechnology and Drug Delivery research team is to create a new generation of drugs with the ability to:

• Improve the pharmaceutical and pharmacological properties of anti-cancer drugs
• Increase the therapeutic efficacy of drug delivery
• Deliver multiple types of therapeutics for combination therapy of cancer and neurodegenerative disorders, such as anti-Alzheimer's diagnostic and therapeutic nanodrugs

We are studying the therapeutic properties of the Polycefin™ family of nanodrugs and imaging agents and their delivery through the BBB. In experimental models, these nanodrugs were proven to be effective in treating gliomas, breast cancers and brain metastasis from primary lung and breast tumors. Examining the pharmacological properties of these nanodrugs showed lack of toxicity lower than the U.S. Food and Drug Administration guideline. This technology shows promise in blocking a combination of unique markers simultaneously, providing a synergistic treatment effect.

One area of research is drug designing to treat different primary and metastatic tumors. We are studying the tumor environment and its interactions mechanisms to discover novel cancer treatments as well as determine toxicology of nanodrugs and imaging agents. Our focus includes nanodrug development for future clinical usage, and novel technology development for treatment of Alzheimer's disease.

We are investigating a natural biopolymer, polymalic acid, from the slime mold Physarum polycephalum as a multifunctional biodegradable and nontoxic molecular platform for a family of anti-cancer and neurodegenerative disorders nanodrugs. Our research goal is to create mini-nanodrugs through these studies for easy tissues delivery and treatments of numerous brain pathological conditions. In addition, we are designing MRI nanoimaging and contrast reagents capable of differentiating brain metastasis, based on tumor specific biomarkers, from other MRI enhancements such as infection, inflammation, necrosis and stroke.

We are studying the molecular mechanisms of nanodrug and nano imaging agents delivery throughout multiple biological barriers and different classes of chemo-therapeutics as a part of the nanodrug in experimental models. So far, investigators have shown that delivery of these nanomedicines through the BBB provide effective diagnostic and therapeutic treatment of brain disorders.

• Principal Investigator: Rameshwar Patil, PhD

We are investigating design, synthesis and optimization of novel nanoconjugates for the delivery of anti-cancer drugs. One research area is the treatment of primary brain tumor and breast tumor, and metastatic brain tumor using nanomedicine. Additional studies include the development of methodology of cancer targeting with peptide, designing and optimization of novel imaging techniques based on nanomedicine for the early detection of tumor, delivery of nanoconjugates across BBB for treatment and detection of neurological disorders and syntheses and development of immune-nanoconjugates for anti-cancer treatment.

• Principal Investigator: Hui Ding, PhD

We are studying the role of tumor microenvironment in cancer development and devising a new concept of nano-immunotherapy to improve the efficacy and expand the indication of current immunotherapy paradigm. Our investigations include researching novel approaches (immune checkpoint inhibition; CRISPR/Cas9 based gene editing; cell engineering as well as biochemical approaches) to activate the immune function to fight cancer.

• Principal Investigator: Tao Sun, PhD

Nanotechnology and Drug Delivery research is multidisciplinary, combining collaborations across a number of Cedars-Sinai divisions, including:

• Biomedical Imaging Research Institute
• Cancer
• Department of Biomedical Sciences
• Medicine Department
• Pathology and Laboratory Medicine
• Surgery
• Women's Health

Through these internal collaborations, we design drugs in the laboratory and test them in experimental models.

In addition, Nanotechnology and Drug Delivery has ongoing external collaborations with:

• Surgical Oncology, UCLA Department of Surgery
• UCLA Molecular Biology Institute
• Koch Institute for Integrative Cancer Research at MIT

The Cedars-Sinai Nanotechnology and Drug Delivery research area hosts a biannual Nanomedicine for Imaging and Treatment Conference, bringing together scientists from across the world to discuss the latest in preclinical and clinical advances in the treatment of cancer, neurodegenerative disorders and other pathological conditions.