Integrated Cancer Research Center Seminar

Event Details
  • Date/Time:
    • Tuesday April 28, 2015
      4:00 pm - 5:00 pm
  • Location: Parker H. Petit Institute for Bioengineering & Bioscience, Room 1128
  • Phone: (404) 894-6228
  • URL: http://www.petitinstitute.gatech.edu
  • Email:
  • Fee(s):
    N/A
  • Extras:
Contact

John McDonald, PhD

Summaries

Summary Sentence: "Polymeric Micelles – A Transformative Technology at the Clinical Stage" - Alexander Kabanov, PhD, DrSci - University of North Carolina, Chapel Hill

Full Summary: Georgia Tech has been a leader in the development of collaborative approaches to both cancer diagnostics and therapeutics. The mission of the Integrated Cancer Research Center (ICRC) is to facilitate integration of the diversity of technological, computational, scientific and medical expertise at Georgia Tech and partner institutions in a coordinated effort to develop improved cancer diagnostics and therapeutics.

Media
  • Integrated Cancer Research Center Integrated Cancer Research Center
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"Polymeric Micelles – A Transformative Technology at the Clinical Stage"

Alexander Kabanov, PhD, DrSci
Director, Center for Nanotechnology in Drug Delivery
Mescal S. Ferguson Distinguished Professor
Codirector, Carolina Institute for Nanomedicine
University of North Carolina at Chapel Hill


Polymeric micelle drug carriers were invented a quarter of century ago.1 Today this technology has reached a clinical stage. Nearly a dozen of drug candidates based on polymeric micelles undergo clinical trials and one product, Genexol-PM, a polymeric micelle paclitaxel, was approved for cancer therapy in South Korea.2 The value proposition of currently developed polymeric micelle drugs include increased drug solubility, increased extravasation and targeting to disease sites (e.g. tumors) as well as increased drug activity with respect to multidrug resistant cancers and cancer stem cells (CSC). One class of polymeric micelles is small aggregates (10 to 100 nm) formed by amphiphilic block copolymers. Hydrophobic drug molecules incorporate in polymeric micelles through cleavable covalent bonds or non-covalent interactions. Latest developments in this field include poly(2-oxazoline)-based polymeric micelles that can carry unprecedented high loading of hydrophobic drugs, such as paclitaxel, as well as blends of several insoluble drugs.3 Such formulations have much lower toxicity compared to conventional formulations, which use high amounts of unsafe excipients to dissolve poorly soluble drugs. Consequently, novel polymeric micelle formulations can be administered at much greater doses and are more efficient in killing cancer cells. Another class of polymeric micelles incorporates charged drug molecules and macromolecules by forming electrostatic complex with ionic block copolymers. In this format the incorporated molecules entrap into the polyion complex cores of micelles where they are protected from the biological environment by non-ionic water-soluble polymeric micelle shell. Upon reaching the target destination the micelles disintegrate and released their payload. This technology originally developed for antisense oligonucleotides,4 is now being used with chemotherapeutic agents, pDNA, siRNA and proteins. For example, extensive studies focus on the use of such systems for delivery of therapeutic enzymes (nanozymes) to the brain and other disease sites. In selected cases the nanozymes or are loaded into macrophages, which safely transport them, release at the sites of inflammation during disease.5 Moreover, the macrophages were shown to transduce the nanozyme particles as well as deliver genes into the host cells at the disease site.6 The proof of the principle has been obtained using animal models of stroke, hypertension, Parkinson’s disease, eye inflammation, influenza virus infection, spinal cord injury, and other diseases. Recent work was supported by NIH (U01 CA151806, R01CA184088, R01 CA89225, R01 NS051334, P20 RR021937), NC TraCS (4DR11404), DoD (W81XWH-09-1-0386, W81XWH-10-1-0806, W81XWH-11-1-0700), Rettsyndrome.org (HeART Award #3112) and Ministry of Education and Science of Russian Federation (11.G34.31.0004).

References:
1 H. Bader et al. Angew. Macromol. Chem. 1984, 123/124:457; A. Kabanov et al. FEBS Lett. 1989, 258:343; M. Yokoyama et al. Cancer Res. 1990, 50:1693.
2 M. Yokoyama et. al. J. Exp. Clin. Med. 2011, 3:8.
3 R. Luxenhofer et al. Biomaterials 2010, 31:4972; Y. Han et al. Mol. Pharmaceutics 2012, 9:2302; A. Schulz, et al. ACS Nano 2014, 8 (3), 2686–96.
4 A. Kabanov et al. Bioconj. Chem. 1995, 6: 639; A. Harada and K. Kataoka, Macromolecules 1995, 28: 5294.
5 A.M. Brynskikh et al., Nanomedicine 2010, 5:379-96; M.J. Haney, et al. Nanomedicine 2011, 6:1215.
6 M.J. Haney, et al., PLoS ONE 2013, 8(4): e61852; Y. Zhao, et al. PLoS One 2014, 9(9):e106867.


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Additional Information

In Campus Calendar
Yes
Groups

Parker H. Petit Institute for Bioengineering and Bioscience (IBB)

Invited Audience
Undergraduate students, Faculty/Staff, Graduate students
Categories
Seminar/Lecture/Colloquium
Keywords
graduate students, IBB, ICRC Seminar
Status
  • Created By: Colly Mitchell
  • Workflow Status: Published
  • Created On: Jan 8, 2015 - 11:00am
  • Last Updated: Apr 13, 2017 - 5:20pm