Doble synergetic anticancer activity through a combined chemo-photodynamic therapy and bioimaging of a novel Cas-ZnONPs all-in-one system

J Inorg Biochem. 2024 Sep:258:112623. doi: 10.1016/j.jinorgbio.2024.112623. Epub 2024 May 28.

Abstract

A strategy for cancer treatment was implemented, based on chemo-photodynamic therapy, utilizing a novel formulation, low-cost system called Cas-ZnONPs. This system consisted of the incorporation of Casiopeina III-ia (CasIII-ia), a hydrophilic copper coordination compound with well-documented anti-neoplastic activity, on Zinc oxide nanoparticles (ZnONPs) with apoptotic activity and lipophilicity, allowing them to permeate biological barriers. Additionally, ZnONPs exhibited fluorescence, with emission at different wavelengths depending on their agglomeration and enabling real-time tracking biodistribution. Also, ZnONPs served as a sensitizer, generating reactive oxygen species (ROS) in situ. In in vitro studies on HeLa and MDA-MB-231 cell lines, a synergistic effect was observed with the impregnated CasIII-ia on ZnONPs. The anticancer activity had an increase in cellular inhibition, depending on the dose of exposure to UV-vis irradiation. In in vivo studies utilized zebrafish models for xenotransplanting stained MDA-MB-231 cells and testing the effectiveness of Cas-ZnONPs treatment. The treatment successfully eliminated cancer cells, both when combined with Photodynamic Therapy (PDT) and when used alone. However, a significantly higher concentration (50 times) of Cas-ZnONPs was required in the absence of PDT. This demonstrates the potential of Cas-ZnONPs in cancer treatment, especially when combined with PDT.

Keywords: Bioimaging; Cancer; Casiopeinas; Copper; Photodynamic therapy; Synergic activity.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Copper / chemistry
  • HeLa Cells
  • Humans
  • Nanoparticles / chemistry
  • Photochemotherapy* / methods
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Zebrafish*
  • Zinc Oxide / chemistry
  • Zinc Oxide / pharmacology

Substances

  • Antineoplastic Agents
  • Zinc Oxide
  • Reactive Oxygen Species
  • Photosensitizing Agents
  • Coordination Complexes
  • Copper