Self-Stimulated Photodynamic Nanoreactor in Combination with CXCR4 Antagonists for Antileukemia Therapy

ACS Appl Mater Interfaces. 2024 May 1;16(17):21610-21622. doi: 10.1021/acsami.4c01603. Epub 2024 Apr 22.

Abstract

The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models. To fulfill our design, we utilized the CXCR4/CXCL12 biological axis and biomimetic cell membranes in conjunction with self-stimulated phototherapy. This nanoreactor possesses the capability to migrate into the bone marrow cavity, inhibit AML cells from infiltrating into the visceral organ, significantly enhance the antileukemia effect, and prolong the survival time of leukemic mice. Therefore, this nanoreactor has significant potential for achieving high success rates and low recurrence rates in leukemia treatment.

Keywords: CXCR4/CXCL12 biological axis; acute myeloid leukemia; biomimetic cell membranes; nanoreactor; self-stimulated phototherapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Chemokine CXCL12 / metabolism
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / pathology
  • Leukemia, Myeloid, Acute* / therapy
  • Mice
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Receptors, CXCR4* / antagonists & inhibitors
  • Receptors, CXCR4* / metabolism

Substances

  • Receptors, CXCR4
  • Photosensitizing Agents
  • Chemokine CXCL12
  • Antineoplastic Agents
  • CXCR4 protein, human