Targeted dendrimers for antagonizing the migration and viability of NALM-6 lymphoblastic leukemia cells

Bioorg Chem. 2021 Feb;107:104601. doi: 10.1016/j.bioorg.2020.104601. Epub 2021 Jan 1.

Abstract

Acute lymphoblastic leukemia (ALL) or white blood cell cancer is one of the major causes that kills many children worldwide. Although various therapeutic agents are available for ALL treatment, the new drug discovery and drug delivery system are needed to improve their effectiveness, to reduce the toxicity and side-effect, and to enhance their selectivity to target cancer cells. CXCR4 is a protein expressed on the surface of various types of cancer cell including ALL. In this work, the CXCR4-targeted PAMAM dendrimer was constructed by conjugating G5 PAMAM with a CXCR4 antagonist, LFC131. The results revealed that the LFC131-conjugated G5 PAMAM selectively targeted CXCR4 expressing leukemic precursor B cells (NALM-6) and the migration of NALM-6 cells induced by SDF-1α was inhibited at non-cytotoxic concentration. Further research based on this findings may contribute to potential anti-metastatic drugs for lymphoblastic leukemia.

Keywords: Acute lymphoblastic leukemia; LFC131; Migration; NALM-6; PAMAM dendrimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Receptors, CXCR4 / antagonists & inhibitors
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Dendrimers
  • Receptors, CXCR4