Targeting CDK1 and copper homeostasis in breast cancer via a nanopolymer drug delivery system

Cell Biol Toxicol. 2024 Dec 26;41(1):16. doi: 10.1007/s10565-024-09958-2.

Abstract

The prevalence of breast cancer (BRCA) is notable in the female population, being a commonly diagnosed malignancy, where the management of copper levels is crucial for treatment success. This research aims to explore the influence of copper homeostasis on BRCA therapy, with a specific focus on the role of Cyclin-Dependent Kinase 1 (CDK1) and its relationship to copper regulation. A novel thermosensitive hydrogel incorporating nanoparticles (NPs) was engineered to synergize with the chemotherapy drug vincristine (VCR) in inhibiting tumor growth and metastasis. Through a comprehensive approach involving bioinformatics analyses, in vitro experiments, and in vivo models, the study identified CDK1 as a significant factor in BRCA progression under copper homeostasis. MBVP-Gel, a novel thermosensitive hydrogel incorporating NPs, was developed to enhance the delivery of chemotherapy drugs and regulate copper homeostasis in breast cancer treatment. The MBVP-Gel, formulated with copper chelation and VCR NPs, effectively suppressed CDK1 expression, thereby restraining BRCA cell growth and metastasis while enhancing the therapeutic impact of VCR. This investigation offers fresh insights and experimental validation on the interaction between copper homeostasis and BRCA, providing a valuable foundation for refining future treatment strategies. These findings underscore the potential advantages of targeting copper homeostasis and CDK1 in enhancing BRCA therapy, setting the stage for individualized interventions and improved patient consequences.

Keywords: Breast Cancer; Chemoresistance; Copper Homeostasis Regulation; Thermosensitive Hydrogel; Tumor Proliferation Inhibition; Vincristine.

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • CDC2 Protein Kinase* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Copper* / chemistry
  • Copper* / metabolism
  • Copper* / pharmacology
  • Drug Delivery Systems / methods
  • Female
  • Homeostasis* / drug effects
  • Humans
  • Hydrogels / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry

Substances

  • Copper
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Hydrogels