Chlorin e6-Loaded Nanostructured Lipid Carriers Targeted by Angiopep-2: Advancing Photodynamic Therapy in Glioblastoma

Adv Healthc Mater. 2025 Jan;14(2):e2402823. doi: 10.1002/adhm.202402823. Epub 2024 Sep 30.

Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor known for its resistance to standard treatments. Despite surgery being a primary option, it often leads to incomplete removal and high recurrence rates. Photodynamic therapy (PDT) holds promise as an adjunctive treatment, but safety concerns and the need for high-power lasers have limited its widespread use. This research addresses these challenges by introducing a novel PDT approach, using chlorin e6 (Ce6) enclosed in nanostructured lipid carriers (Ang-Ce6-NLCs) and targeted to GBM with the angiopep-2 peptide. Remarkably, a single 5-min irradiation session with LEDs at 660 nm and low power density (10 mW cm- 2) proves effective against GBM, while reducing safety risks associated with high-power lasers. Encapsulation improves Ce6 stability and performance in physiological environments, while angiopep-2 targeting enhances delivery to GBM cells, maximizing treatment efficacy and minimizing off-target effects. The findings demonstrate that Ang-Ce6-NLCs-mediated PDT brings about a significant reduction in GBM cell viability, increases oxidative stress, reduces tumor migration, and enhances apoptosis. Overall, such treatment holds potential as a safe and efficient intraoperative removal of GBM infiltrating cells that cannot be reached by surgery, using low-power LED light to minimize harm to surrounding healthy tissue while maximizing tumor treatment.

Keywords: chlorin e6; glioblastoma; nanostructured lipid carriers; photodynamic therapy.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorophyllides*
  • Drug Carriers / chemistry
  • Glioblastoma* / drug therapy
  • Glioblastoma* / pathology
  • Humans
  • Lipids* / chemistry
  • Nanostructures* / chemistry
  • Nanostructures* / therapeutic use
  • Peptides / chemistry
  • Peptides / pharmacology
  • Photochemotherapy* / methods
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Porphyrins* / chemistry
  • Porphyrins* / pharmacology

Substances

  • Chlorophyllides
  • phytochlorin
  • Porphyrins
  • Angiopep-2
  • Lipids
  • Peptides
  • Drug Carriers
  • Photosensitizing Agents

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