Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma

Angew Chem Int Ed Engl. 2019 Mar 4;58(10):3067-3072. doi: 10.1002/anie.201811691. Epub 2019 Jan 9.

Abstract

The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure. The cellular uptake capacity of these double-targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y-shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.

Keywords: meta-iodobenzylguanidine; molecular scaffold; nanomedicine; neuroblastoma; targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine / analogs & derivatives*
  • 3-Iodobenzylguanidine / metabolism
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Delivery Systems
  • Humans
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Molecular
  • Neuroblastoma / diagnostic imaging*
  • Neuroblastoma / drug therapy
  • Neuroblastoma / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins / analysis*
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Optical Imaging

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Norepinephrine Plasma Membrane Transport Proteins
  • 3-Iodobenzylguanidine