Biomedical Engineering; Brain Injuries; Brain Neoplasms; Neurosurgery; 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 Biomaterials, 2014), and protein or peptide-based drugs (unpublished work).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.
Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma
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
Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery
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
Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance
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
Full List of PubMed Publications
- Yu X, Gou X, Wu P, Han L, Tian D, Du F, Chen Z, Liu F, Deng G, Chen AT, Ma C, Liu J, Hashmi SM, Guo X, Wang X, Zhao H, Liu X, Zhu X, Sheth K, Chen Q, Fan L, Zhou J: Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides. Adv Mater. 2018 Feb; 2018 Jan 8. PMID: 29315863
- Wang T, Hurwitz O, Shimada SG, Tian D, Dai F, Zhou J, Ma C, LaMotte RH: Anti-nociceptive effects of bupivacaine-encapsulated PLGA nanoparticles applied to the compressed dorsal root ganglion in mice. Neurosci Lett. 2018 Feb 1; 2018 Feb 1. PMID: 29355697
- Chen Y, Su M, Li Y, Gao J, Zhang C, Cao Z, Zhou J, Liu J, Jiang Z: Enzymatic PEG-Poly(amine-co-disulfide ester) Nanoparticles as pH- and Redox-Responsive Drug Nanocarriers for Efficient Antitumor Treatment. ACS Appl Mater Interfaces. 2017 Sep 13; 2017 Sep 1. PMID: 28819967
- John SF, Aniemeke E, Ha NP, Chong CR, Gu P, Zhou J, Zhang Y, Graviss EA, Liu JO, Olaleye OA: Characterization of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone as a novel inhibitor of methionine aminopeptidases from Mycobacterium tuberculosis. Tuberculosis (Edinb). 2016 Dec; 2016 Sep 28. PMID: 27856197
- Han L, Cai Q, Tian D, Kong DK, Gou X, Chen Z, Strittmatter SM, Wang Z, Sheth KN, Zhou J: Targeted drug delivery to ischemic stroke via chlorotoxin-anchored, lexiscan-loaded nanoparticles. Nanomedicine. 2016 Oct; 2016 Mar 30. PMID: 27039220
- Chen Z, Patel JM, Noble PW, Garcia C, Hong Z, Hansen JE, Zhou J: A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors. Oncotarget. 2016 Sep 13. PMID: 27494868
- Han L, Kong DK, Zheng MQ, Murikinati S, Ma C, Yuan P, Li L, Tian D, Cai Q, Ye C, Holden D, Park JH, Gao X, Thomas JL, Grutzendler J, Carson RE, Huang Y, Piepmeier JM, Zhou J: Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging. ACS Nano. 2016 Apr 26; 2016 Mar 16. PMID: 26967254
- Chen Y, Gou X, Kong DK, Wang X, Wang J, Chen Z, Huang C, Zhou J: EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF. Oncotarget. 2015 Oct 20. PMID: 26416452
- Cai Q, Chen Z, Kong DK, Wang J, Xu Z, Liu B, Chen Q, Zhou J: Novel microcatheter-based intracarotid delivery approach for MCAO/R mice. Neurosci Lett. 2015 Jun 15; 2015 Apr 18. PMID: 25899778
- Strohbehn G, Coman D, Han L, Ragheb RR, Fahmy TM, Huttner AJ, Hyder F, Piepmeier JM, Saltzman WM, Zhou J: Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance. J Neurooncol. 2015 Feb; 2014 Nov 18. PMID: 25403507
- Sirianni RW, Zheng MQ, Patel TR, Shafbauer T, Zhou J, Saltzman WM, Carson RE, Huang Y: Radiolabeling of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with biotinylated F-18 prosthetic groups and imaging of their delivery to the brain with positron emission tomography. Bioconjug Chem. 2014 Dec 17; 2014 Dec 1. PMID: 25322194
- Ediriwickrema A, Zhou J, Deng Y, Saltzman WM: Multi-layered nanoparticles for combination gene and drug delivery to tumors. Biomaterials. 2014 Nov; 2014 Aug 8. PMID: 25112935
- 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 Jul 16; 2013 Jul 1. PMID: 23818631
- Patel T, Zhou J, Piepmeier JM, Saltzman WM: Polymeric nanoparticles for drug delivery to the central nervous system. Adv Drug Deliv Rev. 2012 May 15; 2011 Dec 20. PMID: 22210134
- Zhou J, Patel TR, Fu M, Bertram JP, Saltzman WM: Octa-functional PLGA nanoparticles for targeted and efficient siRNA delivery to tumors. Biomaterials. 2012 Jan; 2011 Oct 19. PMID: 22014944
- Zhou J, Atsina KB, Himes BT, Strohbehn GW, Saltzman WM: Novel delivery strategies for glioblastoma. Cancer J. 2012 Jan-Feb. PMID: 22290262
- Zhou J, Liu J, Cheng CJ, Patel TR, Weller CE, Piepmeier JM, Jiang Z, Saltzman WM: Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery. Nat Mater. 2011 Dec 4; 2011 Dec 4. PMID: 22138789
- Zhou J, Zhang Y: Preclinical development of cancer stem cell drugs. Expert Opin Drug Discov. 2009 Jul; 2009 Jun 9. PMID: 23489167