Biochemical Basis of Selective Accumulation and Targeted Delivery of Photosensitizers to Tumor Tissues

The method of photodynamic therapy for treatment of malignant neoplasms is based on the selective of accumulation of photosensitizers in the tumor tissue. Insufficient selectivity of photosensitizers in relation to pathologically altered tissues and generalized distribution throughout the body leads to the development of severe toxic effects, including skin phototoxicity. The mechanisms underlying selectivity of photosensitizers for tumor tissue include selective binding to blood proteins and lipoproteins (considering that the number of receptors for those is increased on tumor cell membranes), uptake by macrophages, better solubility at low pH (acidic pH is characteristic of tumor cells), and other mechanisms. At present, increase in the efficiency of photodynamic therapy is largely associated with the additional targeting of photosensitizers to tumor tissues. Targeted delivery strategies are based on the differences in metabolism and gene expression profiles between the tumor and healthy cells. There are differences in expression of receptors, proteases, or transmembrane transporters in these cells. In particular, accelerated metabolism in many types of tumors leads to overexpression of receptors for epidermal growth factor, folic acid, transferrin, and a number of other compounds. This review considers biochemical basis for the selective accumulation of various classes of photosensitizers in tumors (chlorins, phthalocyanines, 5-aminolevulinic acid derivatives, etc.) and discusses various strategies of targeted delivery with emphasis on conjugation of photosensitizers with the receptor ligands overexpressed in tumor cells.

Automated summary

Photodynamic therapy relies on the selective accumulation of photosensitizers in tumor tissues for the treatment of malignant neoplasms. Various mechanisms, including binding to blood proteins, uptake by macrophages, and better solubility at low pH, contribute to the selectivity of photosensitizers for tumor tissues. Targeted delivery strategies take advantage of the differences in metabolism and gene expression profiles between tumor cells and healthy cells, resulting in improved efficiency of photodynamic therapy.