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【10th.July】Biomimetic Nanotechnology for Improved Cancer Diagnosis, Prognosis, and Treatment

2018-07-09


题目:Biomimetic Nanotechnology for Improved Cancer Diagnosis, Prognosis, and Treatment
报告人:Professor Seungpyo Hong, Ph.D.Pharmaceutical Sciences Division, School of Pharmacy;Carbone Comprehensive Cancer Center, School of Medicine and Public Health University of Wisconsin - Madison
时间:2018年7月10日下午3点
地点:化学楼B楼410
邀请人:董常明 教授


BIOGRAPHICAL SKETCH
Professor Seungpyo Hong,Professor of Pharmaceutical Sciences,


FIELD OF STUDY
Hanyang University, Seoul, Korea B.S. 02/1999 Fiber & Polymer Engineering
Hanyang University/Korea Institute of Science and Technology (KIST), Seoul, Korea M.S. 02/2001 Polymer Engineering
University of Michigan, Ann Arbor, MI Ph.D. 08/2006,Macromolecular Science and Engineering
Massachusetts Institute of Technology (MIT),Cambridge, MA Postdoctoral 06/2008 Chemical Engineering


Positions and Honors

Positions and Employment
2001-2002 Research Scientist, Polymer Hybrids Research Center, Korea Institute of Science and Technology (KIST), Seoul, KOREA
2008-2014 Assistant Professor, Department of Biopharmaceutical Sciences, University of Illinois, Chicago,IL
2008-2016 Member, University of Illinois Cancer Center, Chicago, IL
2012-2013 Associate Editor, Journal of Nanopharmaceutics and Drug Delivery, American Scientific Publishers
2014- Co-founder and President, Capio Biosciences, Inc., Madison, WI
2014-2016 Associate Professor, Department of Biopharmaceutical Sciences, University of Illinois, Chicago,IL
2014-2016 Director of Graduate Education for the College of Pharmacy, University of Illinois, Chicago, IL
2016- Associate Editor, Nanomedicine: Nanotechnology, Biology and Medicine, Elsevier
2016- Professor, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin,Madison, WI
2017- Member, Carbone Comprehensive Cancer Center, School of Medicine and Public Health,University of Wisconsin, Madison, WI

Other Selected Experience and Professional Memberships
2004- Member, American Chemical Society (ACS)
2008- Member, American Association for Pharmaceutical Scientists (AAPS)
2008-2012 Member, American Association for Cancer Research (AACR)
2002-2009 Member, Materials Research Society (MRS)
2013- Member, Controlled Release Society (CRS)
2010- NSF Panel Reviewer, NanoManufacturing Program, Division of Civil, Mechanical and Manufacturing Innovation (CMMI); Biomedical Engineering Program (BME), Division of Chemical, Bioengineering, Environmental and Transport Systems (CBET); NanoBioSensing Program, CBET
2010- Ad Hoc Reviewer, Emerging Technologies and Training in Neurosciences (ETTN) Integrated Review Group, National Institutes of Health (NIH); ZRG1 EMNR0W (10) study section, NIH
2011- Breast Cancer Research Program (BCRP) Review Panel, Department of Defense (DOD)
2012- Editorial Board Member, Frontiers in Chemistry; Nanomedicine: NBM; Journal of Nanopharmaceutics and Drug Delivery; Molecules Honors
2002 Dwight F. Benton Fellowship, College of Engineering, University of Michigan, Ann Arbor, MI
2004 Charles G. Overberger Award (The best student award of the year in the field of polymer sciences), Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI
2005 Best Poster Award, 2005 Materials Research Society (MRS) National Fall Meeting, Boston, MA
2007 A 2006 Most-Cited ACS Journal Article, S. Hong et al., Bioconjugate Chem. 2006, 17, 728.
2010 Vahlteich Research Award, University of Illinois College of Pharmacy, Chicago, IL
2012 AAPS New Investigator Award in Pharmaceutics and Pharmaceutical Technologies, American Association of Pharmaceutical Scientists (AAPS)
2013 UIC Researcher of the Year – Rising Star Award, University of Illinois at Chicago, Chicago, IL
2013 Invited Participant, NAE EU-US Frontiers of Engineering Symposium, Chantilly, FRNCE, National Academy of Engineering


Contribution to Science
My early contributions to the related drug delivery fields can be highlighted by a series of papers (the 4 papers listed below have been cited over 1,700 times in total) that reported fundamental understanding of poly(amidoamine) (PAMAM) dendrimer interactions with lipid bilayers and cell membranes. Part of my PhD study revealed, for the first time, that positively charged PAMAM dendrimers can create nanoscale holes in cell membranes, inducing transient enzyme leakage and cell entry of dendrimers. The multivalent binding mediated by folate (FA)-targeted dendrimers was also quantitatively measured for the first time using surface plasmon resonance (SPR). This study demonstrated that the dendrimer-FA conjugates displayed significant enhancement (by orders of magnitude up to 100,000 time lower KD) in binding kinetics compared to free FA, which likely led to the enhanced cancer cell targeting achieved by the targeted dendrimers.

a. S. Hong, A.U. Bielinska, A. Mecke, B. Keszler, J.L. Beals, X. Shi, L. Balogh, B.G. Orr, J.R. Baker & M.M. Banaszak Holl* (2004). The Interaction of Polyamidoamine (PAMAM) Dendrimers with Supported Lipid Bilayers and Cells: Hole Formation and the Relation to Transport. Bioconjugate Chemistry, 15(4),774-782. 15264864.
b. S. Hong, P.R. Leroueil, E.K. Janus, J.L. Peters, M.M. Kober, M.T. Islam, B.G. Orr, J.R. Baker & M.M.Banaszak Holl* (2006) Interaction of polycationic polymers with supported lipid bilayers and cells: nanoscale hole formation and enhanced membrane permeability. Bioconjugate Chemistry, 17(3), 728-734. 16704211.
c. S. Hong, P.R. Leroueil, I.J. Majoros, B.G. Orr, J.R. Baker* & M.M. Banaszak Holl* (2007). The Binding Avidity of A Nanoparticle-Based Multivalent Targeted Drug Delivery Platform. Chem. Biol., 14(1), 107- 115. 17254956.
d. S. Hong, R. Rattan, I.J, Majoros, D.G. Mullen, J.L. Peters, X. Shi, A.U. Bielinska, L. Blanco, B.G. Orr,J.R. Baker & M.M. Banaszak Holl* (2009). The Role of Gaglioside GM1 in Cellular Internalization Mechanisms of Poly(amidoamine) Dendrimers. Bioconjugate Chem., 20(8), 1503-1513. 19583240.PMCID: PMC4641442
1,
With the knowledge and experience obtained from my early studies on dendrimers, we have designed a new type of nanocarriers that are based on dendron block copolymers, which was first synthesized in my lab.Owing to the unique dendron structure, the dendron micelles exhibited an ultralow critical micelle concentration (CMC) in the order of ~10 nM, improved surface coverage by PEG layers, and modularity in their cell interactions (both non-specific and specific) controlled by the PEG chain lengths and density. Our dendron micelles represent a promising new class of nanocarriers, offering a new platform technology.
a. J.W. Bae, R.M. Pearson, N. Patra, S. Sunoqrot, L. Vukovic, P. Kral & S. Hong* (2011). Dendronmediated Self-Assembly of Highly PEGylated Block Copolymers. Chem. Commun., 47(37), 10302-10304. 21858356. PMCID: PMC3190671
b. H.-J. Hsu, S. Sen, R.M. Pearson, P. Kral & S. Hong* (2014). Poly(ethylene glycol) Corona Chain Length Controls End-group-dependent Cell Interactions of Dendron Micelles. Macromolecules, 47,6911-6918. 25709141. PMCID: PMC4334293
c . R.M. Pearson, S. Sen, H.-J. Hsu, M. Pasko, M. Gaske, P. Kral & S. Hong* (2016). Tuning the Selectivity of Dendron Micelles through Variations of the Poly(ethylene glycol) Corona. ACS Nano,10(7), 6905-6914. 27267700.
d . H.J. Hsu, Y. Han, M. Cheong, P. Kral & S. Hong* (2018). Dendritic PEG Outer Shells Enhance Serum Stability of Polymeric Micelles. Nanomedicine: NBM, 14, 1879-1889. 29782948.
2,
We have also designed and developed another novel drug delivery platform through integration of dendrimers and polymeric nanoparticles (NPs), term as hybrid NPs. The hybrid NPs, consisting of targeted PAMAM dendrimers encapsulated in PLA-PEG NPs, have demonstrated the combined advantages of two nanocarriers,achieving kinetically controlled cancer cell targeting as well as improved tumor penetration and pharmacokinetics.
a. S. Sunoqrot, J.W. Bae, S.E. Jin, R.M. Pearson, Y. Liu & S. Hong* (2011). Kinetically Controlled Cellular Interactions of Polymer-Polymer and Polymer-Liposome Nanohybrid Systems. Bioconjugate Chem.,22(3), 466-474. 21344902. PMCID: PMC3059376
b. S. Sunoqrot, J.W. Bae, R.M. Pearson, K. Shyu, Y. Liu, D.H. Kim & S. Hong* (2012). Temporal Control over Cellular Targeting through Hybridization of Folate-targeted Dendrimers and PEG-PLA Nanoparticles. Biomacromolecules, 13(4), 1223-1230. 22439905. PMCID: PMC3329776
c. S. Sunoqrot, J. Bugno, D. Lantvit, J.E. Burdette & S. Hong* (2014) Prolonged Blood Circulation and Enhanced Tumor Accumulation of Folate-targeted Dendrimer-Polymer Hybrid Nanoparticles. J. Control. Release, 191, 115-122. 24837188. PMCID: PMC4156894
d. J. Bugno, H.J. Hsu, R.M. Pearson, H. Noh & S. Hong* (2016) Size and Surface Charge of Engineered Poly(amidoamine) Dendrimers Modulate Tumor Accumulation and Penetration: A model study using multicellular tumor spheroids. Mol. Pharm., 13(7), 2155-2163. 26828309.
3,
We have explored topical, transdermal delivery applications using dendrimers and dendron micelles, in an effort of locally delivering chemopreventive medicine, such as endoxifen, to reduce its toxic side effects often observed when systemically exposed. We have shown that the skin interactions of PAMAM dendrimers can be engineered by size, surface charge, and hydrophobicity of dendrimers. In addition, we have demonstrated that PAMAM dendrimers are an effective platform for gene delivery (particularly miRNA) to effective target and treat leukemic cells.
a. Y. Yang, S. Sunoqrot, C. Stowell, J. Ji, C.W. Lee, J.W. Kim, S.A. Khan & S. Hong* (2012). Effect of Size, Surface Charge, and Hydrophobicity of Poly(amidoamine) Dendrimers on Their Skin Penetration.Biomacromolecules, 13(7), 2154-2162. 22621160. PMCID: PMC3392468
b . Y. Yang, J. Bugno & S. Hong* (2013). Nanoscale Polymeric Penetration Enhancers in Topical Drug Delivery. Polym. Chem., 4, 2651-2657.
c. Y. Yang, R.M. Pearson, O. Lee, C.-W. Lee, R.T. Chatterton, S.A. Khan & S. Hong* (2014). Dendronbased Micelles for Topical Delivery of Endoxifen: A potential chemo-reventive medicine for breast cancer. Adv. Func. Mater., 24(17), 2441-2449.
d. X. Jiang, C. Hu, S. Arnovitz, J. Bugno, M. Yu, Z. Zuo, P. Chen, H. Huang, B. Ulrich, C. Hu, S.Gurbuxani, H. Weng, J. Strong, Y. Wang, Y. Li, J. Salat, S. Li, A.G. Elkahloun, Y. Yang, M.B. Neilly,R.A. Larson, M.M. Le Beau, T. Herold, S.K. Bohlander, P.P. Liu, J. Zhang, Z. Li, C. He, J. Jin, S. Hong,& J. Chen* (2016) miR-22 Plays a Potent Anit-Tumor Role with Therapeutic Potential in Acute Myeloid Leukemia. Nat. Commun., 7, 11452. 27116251. PMCID: PMC5477496
4,
Most relevant to this proposal, my lab has developed a new capture platform for effective detection and isolation of circulating tumor cells (CTCs). Our approach is unique and highly innovative in that we use the biomimetic combination of cell rolling and multivalent binding achievable through application of the nanoengineering approach. Our results have shown that the capture surface achieved up to 1 million-fold enhancement in binding kinetics and over 150-fold enhancement in capture efficiency, compared to the surface capturing CTCs using antibodies only. We are currently conducting a few clinical pilot studies to validate our novel system using clinical blood specimens from head and neck, prostate, and breast cancer patients.
a. J.H. Myung, K.A. Gajjar, J. Saric, D.T. Eddington & S. Hong* (2011). Dendrimer-mediated Multivalent Binding for Enhanced Capture of Tumor Cells. Angew. Chem. Int. Ed., 50(49), 11769-11772.22012872. PMCID: PMC3549433
b. J.H. Myung, K.A. Gajjar, J. Chen, R.E. Molokie & S. Hong* (2014). Differential Detection of Tumor Cells using a Combination of Cell Rolling, Multivalent Binding, and Multiple Antibodies. Anal. Chem., 86(12),6088-6094. 24892731. PMCID: PMC4066911
c. J.H. Myung, M. Roengvoraphoj, K.A. Tam, T. Ma, V.A. Memoli, E. Dmitrovsky, S.J. Freemantle & S.Hong* (2015). Effective Capture of Circulating Tumor Cells from a Transgenic Mouse Lung Cancer Model using Dendrimer Surfaces Immobilized with anti-EGFRs. Anal. Chem., 87(19), 10096-10102.26312815. PMCID: PMC4734638
d. J.H. Myung, M.J. Eblan, J.M. Caster, S.J. Park, M.J. Poellmann, K. Wang, K.A. Tam, S.M. Miller, C.Shen, R.C. Chen, T. Zhang, J.E. Tepper, B.S. Chera, A.Z. Wang* & S. Hong* (2018). Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture. Clin. Cancer Res., 24(11), 2539-2547. 29545463. PMCID: PMC5984698


Research Support
Ongoing Research Support
NSF Hong (PI) 08/01/14-09/30/18 DMR-1409161/1741560
NSF Hong (PI) 08/01/18-09/30/21DMR-1808251 (recommended for funding, pending final approval)
Industry Sponsored Research Hong (PI) 11/01/17-10/31/20 SRA/Capio Biosciences, Inc.
NCI/NIH Miller (PI) 11/01/18-04/30/19 1R43CA232924-01 (recommended for funding, pending final approval)
NCI/NIH Chen (PI) 01/01/14-12/31/18 1R01CA182528 01
NIBIB/NIH Gemeinhart (PI) 07/16/16-07/15/18 1R21EB022374
NIAMS/NIH Moore (PI) 05/01/17-04/30/20 1R01AR069541



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