Polymalic acid-based nano biopolymers for targeting of multiple tumor markers: an opportunity for personalized medicine?

J Vis Exp. 2014 Jun 13:(88):50668. doi: 10.3791/50668.

Abstract

Tumors with similar grade and morphology often respond differently to the same treatment because of variations in molecular profiling. To account for this diversity, personalized medicine is developed for silencing malignancy associated genes. Nano drugs fit these needs by targeting tumor and delivering antisense oligonucleotides for silencing of genes. As drugs for the treatment are often administered repeatedly, absence of toxicity and negligible immune response are desirable. In the example presented here, a nano medicine is synthesized from the biodegradable, non-toxic and non-immunogenic platform polymalic acid by controlled chemical ligation of antisense oligonucleotides and tumor targeting molecules. The synthesis and treatment is exemplified for human Her2-positive breast cancer using an experimental mouse model. The case can be translated towards synthesis and treatment of other tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Female
  • Gene Silencing
  • Humans
  • Malates / administration & dosage*
  • Malates / chemical synthesis
  • Malates / chemistry
  • Malates / metabolism
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy / methods*
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / genetics
  • Physarum polycephalum / genetics
  • Physarum polycephalum / metabolism
  • Polymers / administration & dosage*
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Polymers / metabolism
  • Precision Medicine / methods
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Malates
  • Oligonucleotides, Antisense
  • Polymers
  • poly(malic acid)
  • ERBB2 protein, human
  • Receptor, ErbB-2