Brain Injuries; Brain Neoplasms; Genetic Therapy; Drug Delivery Systems; Stroke; Nanomedicine; Cell- and Tissue-Based Therapy
Our research focuses on developing novel nanomedicine and stem cell therapies for treatment of neurological disorders.
Specialized Terms: Nanomedicine; Brain cancer; Stroke; Traumatic brain injury; Drug delivery; Gene therapy; Stem cell therapy;
Extensive Research Description
Drug delivery to the brain is a major challenge, because the brain possesses the blood brain barrier (BBB), which strictly limits transport of most agents into the brain through intravenous administration. Our prior efforts have focused on developing a locoregional approach for image-guided drug delivery to the brain using brain-penetrating nanoparticles (Zhou J. et al, PNAS, 2013; Strohbehn G. et al. J Neurooncol. 2014), which is mature for a possible clinical testing in near future. Recently, we shifted our efforts to develop next generation nanotechnology for systemic drug delivery to the brain and have made promising progress. With our new delivery techniques, we have demonstrated the possibility to intravenously deliver pharmacologically significant quantities of therapeutic agents to the brain for treatment of a variety of brain diseases, including brain cancer, brain metastases, ischemic stroke and traumatic brain injury. We are currently optimizing these systems for further enhanced specificity and efficiency.
Along with the development of techniques for drug delivery to the brain, we design nanoparticles for efficient delivery of a variety of cargo agents, including small molecule drugs (Zhou J. et al, PNAS, 2013), contrast agents or tracers for imaging (Zhou J. et al, PNAS, 2013; Strohbehn G. et al. J Neurooncol. 2014), genetic materials for gene therapy (Zhou. et al. Nature Materials, 2011; Zhou J. et al. Biomaterials, 2012; Ediriwickrema A. et al. Biomaterials, 2014), and protein or peptide-based drugs (unpublished work).
We are also interested in engineering neural stem cells for disease treatment. In particular, we aim to combine the most recent advances in induced pluripotent stem cell (iPS) technology and emerging nanotechnology to develop personalized combination therapies for treatment of neurological disorders. We have made interesting progress in this research direction.
- Zhou J, Patel TR, Sirianni RW, Strohbehn G, Zheng MQ, Duong N, Schafbauer T, Huttner AJ, Huang Y, Carson RE, Zhang Y, Sullivan DJ Jr, Piepmeier JM, Saltzman WM. Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proc Natl Acad Sci U S A. 2013
- Zhou J, Liu J, Jiang Z, Patel T, Weller C, Piepmeier JM, Saltzman WM, Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery, Nature Materials, 2011, 11(1):82-90
- Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Margolick JB, Liotta LA, Petricoin III E, and Zhang Y. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A, 2007, 41(104):16158-63