Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities - PubMed (original) (raw)

Review

Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

Malini Olivo et al. Pharmaceuticals (Basel). 2010.

Abstract

Photodynamic therapy (PDT) has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS), which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS), that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body's immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

Keywords: anti-angiogenesis; immune response; nanoparticles; peptides; photodynamic therapy (PDT); targeted therapy; vascular PDT.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Design of photosensitizer conjugate: (a) peptides covalently attached to a photosensitizer via linker, (b) several peptides as well as photosensitizer molecules conjugated to a polymer scaffold, and (c) peptides covalently coupled to liposomes encapsulating PS.

Figure 2

Figure 2

(a) Vascular-targeting PDT (VTP) is performed when the PS is confined within the tumor vasculature. Following VTP, the sensitive sites within the microvasculature are damaged thus causing vessel constriction, blood flow stasis and thrombus formation that finally leads to tumor destruction. (b) PDT induced oxidative stress causes hypoxia within the tumor tissue that triggers the release of angiogenic growth factors that include VEGF, COX-2 and EGFR. These pro-angiogenic factors facilitate endothelial cell proliferation and migration thus initiating angiogenesis and tumor growth. Administration of angiogenic inhibitors that specifically target these growth factors in combination with PDT has shown to be effective in suppressing angiogenesis and preventing tumor regrowth.

Similar articles

Cited by

References

    1. Dolmans D.E., Fukumura D., Jain R.K. Photodynamic therapy for cancer. Nat. Rev. Cancer. 2003;3:380–387. - PubMed
    1. Dougherty T.J., Gomer C.J., Henderson B.W., Jori G., Kessel D., Korbelik M., Moan J., Peng Q. Photodynamic therapy. J. Natl. Cancer Inst. 1998;90:889–905. - PMC - PubMed
    1. Fabris C., Valduga G., Miotto G., Borsetto L., Jori G., Garbisa S., Reddi E. Photosensitization with zinc (II) phthalocyanine as a switch in the decision between apoptosis and necrosis. Cancer Res. 2001;61:7495–7500. - PubMed
    1. Henderson B.W., Dougherty T.J. How does photodynamic therapy work? Photochem. Photobiol. 1992;55:145–157. - PubMed
    1. Castano A.P., Mroz P., Hamblin M.R. Photodynamic therapy and anti-tumour immunity. Nat. Rev. Cancer. 2006;6:535–545. - PMC - PubMed

Publication types

LinkOut - more resources