(504d) Conjugation of Anti-HER2 Monoclonal Antibody Onto PLGA-PEG Nanoparticles Using Click Chemistry

Nanoparticles are known to passively target tumor tissue due to the Enhanced Permeability and Retention effect.  Via this phenomenon the particles tend to naturally accumulate in the unhealthy tissue, it is why some cancer drugs have been formed into nano sized particles, allowing doctors to administer three times the dosage as compared to before.  Actively targeted delivery continues to be a struggle.  Antibodies, known as the “magic bullets”, have the most specific targeting abilities.  They also are extremely difficult to work with as they tend to bind to the surface of particles in uncontrolled and unpredictable manners.  Our intention is to create a biologically compatible polymer nanoparticle comprising of PLGA (poly lactic-co-glycolic acid) and PEG (poly ethylene glycol) in the 100-200 nm size range via emulsion method.  PLGA is FDA approved for drug delivery purposes and PEG is widely used in a process called PEGylation to increase systemic circulation.  An anti-HER2 monoclonal antibody will be selected for its ability to target an antigen overexpressed on the surface of most breast cancer cells and covalently attached to the nanoparticles via click chemistry.  Click chemistry is a method that has been shown to be effective for this purpose with other types of nanoparticles and has shown improved efficacy in both ligand attachment and maintaining targeting activities as compared to other methods.  The poly ethylene glycol will be modified to have an azide end group and the antibodies will have to be alkyne functionalized to facilitate the CuAAC, or Copper catalyzed azide-alkyne cycloaddition reaction.  Final system targeting abilities will be tested via protein assay.