Tumor microenvironment adrenergic nerves blockade liposomes for cancer therapy

J Control Release. 2022 Nov:351:656-666. doi: 10.1016/j.jconrel.2022.09.049. Epub 2022 Oct 6.

Abstract

Adrenergic nerves, which are innervated in the tumor, regulate tumor initiation, angiogenesis, and the establishment of the tumor immunosuppressive microenvironment. The study aimed to evaluate the effectiveness of propranolol liposomes (Lipo pro) in inhibiting adrenergic nerve signaling in cancer therapy. Lipo pro significantly regulated the distribution of tumor microenvironment adrenergic nerves, tumor blood vessels, and immunosuppressive microenvironment. Furthermore, it displayed considerable therapeutic effects on prostatic cancer, pancreatic ductal adenocarcinoma, and melanoma. The combination therapeutic regimen, in which Lipo pro was the primary treatment and was supplemented by chemotherapy, showed significant advantages over any single treatment, effectively restraining tumor growth in situ and metastasis, thereby prolonging the survival of mice. This study established a proof-of-concept by targeting tumor adrenergic nerve signaling for cancer therapy.

Keywords: Adrenergic nerves; Combination regimen; Liposome; Propranolol; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / therapeutic use
  • Animals
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Liposomes
  • Mice
  • Pancreatic Neoplasms* / pathology
  • Tumor Microenvironment

Substances

  • Liposomes
  • Adrenergic Agents