Biodegradable Nanoprobe Enables Noninvasive Imaging of Angiogenesis

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Researchers at the University of California have developed a biodegradable nanoprobe that enables noninvasive imaging of angiogenesis, a critical process involved in tumor growth and metastasis. The nanoprobe, designed to target alpha(v)beta(3) integrin receptors, has a modular multivalent core-shell architecture that imparts biological stealth and dictates pharmacokinetics. This innovative design allows for a 50-fold enhancement of binding affinity to alpha(v)beta(3) integrin receptors and a 6-fold increase in receptor-mediated endocytosis.

Key Takeaways:

  • The biodegradable nanoprobe is designed to target alpha(v)beta(3) integrin receptors, a biological marker known to modulate angiogenesis.
  • The nanoprobe has a modular multivalent core-shell architecture, consisting of a biodegradable heterobifunctional dendritic core chemoselectively functionalized with heterobifunctional polyethylene oxide (PEO) chains.
  • The placement of radioactive moieties at the core prevents in vivo dehalogenation, a potential problem for radiohalogens in imaging and therapy.
  • The targeting peptides of cyclic arginine-glycine-aspartic acid (RGD) motifs enhance accessibility to alpha(v)beta(3) integrin receptors.
  • Cell-based assays show a 6-fold increase in alpha(v)beta(3) receptor-mediated endocytosis of the targeted nanoprobe compared with the nontargeted nanoprobe.
  • In vivo biodistribution studies demonstrate excellent bioavailability for the targeted and nontargeted nanoprobes.
  • The nanoprobe enables highly selective imaging of angiogenesis in a murine hindlimb ischemia model.

Statistics:

  • The nanoprobe has a 50-fold enhancement of binding affinity to alpha(v)beta(3) integrin receptors, down from 10.40 nM to 0.18 nM IC50.
  • The nanoprobe shows a 6-fold increase in alpha(v)beta(3) receptor-mediated endocytosis in cell-based assays.
  • In vivo biodistribution studies show excellent bioavailability for the targeted and nontargeted nanoprobes.

Sources:

  • Almutairia, A., et al. "Biodegradable dendritic positron-emitting nanoprobes for the noninvasive imaging of angiogenesis." Proceedings of the National Academy of Sciences of the United States of America, 2009;106(3):685-690.
  • University of California, College Chemical, 718 Latimer Hall, Berkeley, CA 94720, USA.
  • National Acad Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA.