Photochemical delivery of bleomycin induces T-cell activation of importance for curative effect and systemic anti-tumor immunity

J Control Release. 2017 Dec 28;268:120-127. doi: 10.1016/j.jconrel.2017.10.015. Epub 2017 Oct 16.


Photochemical internalization (PCI) is a technology to enhance intracellular drug delivery by light-induced translocation of endocytosed therapeutics into the cytosol. The aim of this study was to explore the efficacy of PCI-based delivery of bleomycin and the impact on systemic anti-tumor immunity. Mouse colon carcinoma cells (CT26.CL25), stably expressing the bacterial β-galactosidase, were inoculated into the legs of athymic or immuno-competent BALB/c mice strains. The mice were injected with the photosensitizer AlPcS2a and bleomycin (BLM) prior to tumor light exposure from a 670nm diode laser. Photochemical activation of BLM was found to induce synergistic inhibition of tumor growth as compared to the sum of the individual treatments. However, a curative effect was not observed in the athymic mice exposed to 30J/cm2 of light while >90% of the thymic mice were cured after exposure to only 15J/cm2 light. Cured thymic mice, re-challenged with CT26.CL25 tumor cells on the contralateral leg, rejected 57-100% of the tumor cells inoculated immediately and up to 2months after the photochemical treatment. T-cells from the spleen of PCI-treated mice were found to inhibit the growth of CT26.CL25 cells in naïve thymic mice with a 60% rejection rate. The results show that treatment of CT26.CL25 tumors in thymic mice by PCI of BLM induces a systemic anti-tumor immunity.

Keywords: Anti-tumor immunity; Bleomycin; Photochemical internalization; Photodynamic.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / therapeutic use
  • Bleomycin / administration & dosage*
  • Bleomycin / therapeutic use
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Female
  • Indoles / administration & dosage*
  • Indoles / therapeutic use
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Organometallic Compounds / administration & dosage*
  • Organometallic Compounds / therapeutic use
  • Photochemotherapy
  • Photosensitizing Agents / administration & dosage*
  • Photosensitizing Agents / therapeutic use
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Tumor Burden / drug effects


  • Antibiotics, Antineoplastic
  • Indoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • Bleomycin
  • aluminum phthalocyanine disulfonate