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

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Abstract

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.

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Abbreviations

5-ALA:

5-aminolevulinic acid

AB:

antibody

AlPc:

aluminum phthalocyanine

AlPcS4:

aluminum phthalocyanine tetrasulfonate

E2:

estradiol

Chl:

chlorin e6

Cur:

curcumin

DME-Chl:

chlorin e6 dimethyl ester

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

FA:

folic acid

G:

glucose

HDL:

high-density lipoproteins

Hy:

hypericin

IC50 :

half maximal inhibitory concentration

LDL:

low-density lipoproteins

LpS:

liposome

BPD-MA:

benzoporphyrin derivative

M:

mannose

NP:

nanoparticle

P:

peptide

Pyro-Pheo:

pyropheophorbide A

PPIX:

protoporphyrin IX

PEG:

polyethylene glycol

Tmf:

tamoxifen

Tf:

transferrin

Tf(P):

peptide binding to transferrin receptors

PDT:

photodynamic therapy

PheoA:

pheophorbide A

Pc:

phthalocyanine

SiPc:

silicon phthalocyanine

Vir:

virosome

ZnPc:

zinc phthalocyanine

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    Veronika I. Ivanova-Radkevich

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Ivanova-Radkevich, V.I. Biochemical Basis of Selective Accumulation and Targeted Delivery of Photosensitizers to Tumor Tissues. Biochemistry Moscow 87, 1226–1242 (2022). https://doi.org/10.1134/S0006297922110025

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