Integration of EMAP-II-targeted anti-angiogenesis and photodynamic therapy using zinc phthalocyanine nanosystem for enhanced cancer treatment

Colloids Surf B Biointerfaces. 2025 Apr:248:114493. doi: 10.1016/j.colsurfb.2024.114493. Epub 2025 Jan 3.

Abstract

Angiogenesis provides essential nutrients and oxygen to tumors during tumorigenesis, facilitating invasion and metastasis. Consequently, inhibiting tumor angiogenesis is an established strategy in anti-cancer therapy. In this study, we engineered a dual-function nanosystem with both antiangiogenic and photodynamic properties. We transformed the hydrophobic photosensitizer zinc phthalocyanine (PS) into a hydrophilic form via protein renaturation, resulting in a novel photosensitizer: Monocyte-Activating Polypeptide-II (EMAP-II:PS@NPs). Characterization through dynamic light scattering (DLS) and UV-vis spectroscopy showed that these nanoparticles exhibited uniform size and stability, and enhanced solubility. We further demonstrated that EMAP-II:PS@NPs effectively target tumor vascular endothelia causing intracellular photodynamic cytotoxicity. Notably, EMAP-II:PS@NPs achieved effective ablation of solid tumors at significantly reduced dosages of drugs compared to conventional therapies, due to their potent apoptotic effects on light-exposed cells. This study highlights the potential of combining anti-angiogenic activity with phototherapy, paving the way for innovative cancer treatment strategies.

Keywords: Angiogenesis; Anti-tumor; EMAP-II; Phthalocyanine.

MeSH terms

  • Angiogenesis Inhibitors* / chemistry
  • Angiogenesis Inhibitors* / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Isoindoles*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Organometallic Compounds* / chemistry
  • Organometallic Compounds* / pharmacology
  • Particle Size
  • Photochemotherapy*
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Surface Properties
  • Zinc Compounds*

Substances

  • Zinc Compounds
  • Zn(II)-phthalocyanine
  • Isoindoles
  • Organometallic Compounds
  • Indoles
  • Photosensitizing Agents
  • Angiogenesis Inhibitors
  • Antineoplastic Agents