Project 2

Evaluation of the Applications of ‘Smart’ Nanoparticles to Cancer Therapy and Imaging

Joseph DeSimone, Ph.D.

Kenan Professor of Chemistry and Chemical Engineering, Project PI

Project 2 is closely linked with Project 1 and will investigate the utilization of nanoparticles fabricated by PRINT technology in cancer diagnosis and therapy. This includes:

  • preparing ‘smart’ nanoparticles linked to cell-targeting peptides or aptamers and studying their interactions with cell targets both in culture and in animals
  • evaluating the ability of ‘smart’ nanoparticles to deliver drugs or therapeutic oligonucleotides to a variety of mouse tumors and examining the impact on tumor growth
  • evaluating the ability of ‘smart’ nanoparticles to deliver imaging agents to a variety of mouse tumors

These activities will make use of the Combinatorial Library Research Core as well as the Pharmacokinetics Core and Small Animal Imaging Core. Although the emphasis will be on nanoparticles prepared by the PRINT technology, this Project will also investigate the inorganic nanoparticles produced by Dr. W. Lin in Project 4 as well as the lipid nanoparticles produced by Dr. Szoka in the Pharmacokinetics Core.

Project 2 will tap into the rich store of mouse models of cancer available through the UNC Lineberger Comprehensive Cancer Center in order to ascertain the most productive ways to apply nanoparticle technology to cancer. The nanoparticles will be evaluated for delivery of imaging or therapeutic moieties in a series of challenging animal models including:

  • delivery of adjuvants for tumor immunity to dendritic cells
  • delivery of splice-correcting antisense oligonucleotides to increase expression of the pro-apoptotic Bcl-Xs protein
  • ‘passive’ delivery of appropriately sized long-circulating nanoparticles to tumors via their leaky vasculature using several mouse models, with MRI imaging of the nanoparticle delivery
  • targeted delivery of nanoparticles to pancreatic tumors expressing the TVA antigen
  • targeted delivery of nanoparticles to clonal myeloma cells using peptides that are recognized by surface immunoglobulin
  • targeted delivery of nanoparticles to Erb2 positive breast tumors using anti-HER2 antibodies or cell targeting peptides or aptamers

These activities will make extensive use of the Animal Models Core to support the various mouse tumor models.

Links:

Professor DeSimone's home page

NSF Science and Technology Center for Environmentally Responsible Solvents and Processes

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
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