Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel

Nanomedicine (Lond). 2015;10(7):1139-47. doi: 10.2217/nnm.14.194.

Abstract

Aim: Effectiveness of Glypican-3 (GPC3)-targeted photoimmunotherapy (PIT) combined with the nanoparticle albumin-bound paclitaxel (nab-paclitaxel) for hepatocellular carcinoma was evaluated.

Materials & methods: GPC3 expressing A431/G1 cells were incubated with a phthalocyanine-derivative, IRDye700DX (IR700), conjugated to an anti-GPC3 antibody, IR700-YP7 and exposed to near-infrared light. Therapeutic experiments combining GPC3-targeted PIT with nab-paclitaxel were performed in A431/G1 tumor-bearing mice.

Results: IR700-YP7 bound to A431/G1 cells and induced rapid target-specific necrotic cell death by near-infrared light exposure in vitro. IR700-YP7 accumulated in A431/G1 tumors. Tumor growth was inhibited by PIT compared with nontreated control. Additionally, PIT dramatically increased nab-paclitaxel delivery and enhanced the therapeutic effect.

Conclusion: PIT targeting GPC3 combined with nab-paclitaxel is a promising method for treating hepatocellular carcinoma.

Keywords: Glypican-3; hepatoma; monoclonal antibody; nab-paxlitaxel; nanodelivery; photocyanine dye; photoimmunotherapy.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Albumins / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Female
  • Glypicans / immunology*
  • Immunotherapy* / methods
  • Liver / drug effects
  • Liver / immunology
  • Liver / pathology
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Mice
  • Mice, Nude
  • Paclitaxel / therapeutic use*
  • Phototherapy* / methods

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents
  • GPC3 protein, human
  • Glypicans
  • Paclitaxel