Porphylipoprotein Accumulation and Porphylipoprotein Photodynamic Therapy Effects Involving Cancer Cell-Specific Cytotoxicity.

Hirofumi Matsui,Hiromu Ito,Hiromi Kurokawa

doi:10.3390/ijms22147306

Abstract

In photodynamic therapy (PDT) for neoplasms, photosensitizers selectively accumulate in cancer tissue. Upon excitation with light of an optimal wavelength, the photosensitizer and surrounding molecules generate reactive oxygen species, resulting in cancer cell-specific cytotoxicity. Porphylipoprotein (PLP) has a porphyrin-based nanostructure. The porphyrin moiety of PLP is quenched because of its structure. When PLP is disrupted, the stacked porphyrins are separated into single molecules and act as photosensitizers. Unless PLP is disrupted, there is no photosensitive disorder in normal tissues. PLP can attenuate the photosensitive disorder compared with other photosensitizers and is ideal for use as a photosensitizer. However, the efficacy of PLP has not yet been evaluated. In this study, the mechanism of cancer cell-specific accumulation of PLP and its cytotoxic effect on cholangiocarcinoma cells were evaluated. The effects were investigated on normal and cancer-like mutant cells. The cytotoxicity effect of PLP PDT in cancer cells was significantly stronger than in normal cells. In addition, reactive oxygen species regulated intracellular PLP accumulation. The cytotoxic effects were also investigated using a cholangiocarcinoma cell line. The cytotoxicity of PLP PDT was significantly higher than that of laserphyrin-based PDT, a conventional type of PDT. PLP PDT could also inhibit tumor growth in vivo.

Highlights

Photodynamic therapy (PDT) for neoplasms has the following three components: a photosensitizer (PS), light, and oxygen [1]
We evaluated the relationship between mitochondrial reactive oxygen species (ROS) and heme carrier protein 1 (HCP1) expression using rat gastric mucosal cells, RGM1, its cancer-like mutants, RGK1, obtained by treatment with carcinogenic chemicals, and manganese superoxide dismutase (MnSOD)-overexpressing RGK cells, RGK-MnSOD
We investigated the effect of PLP PDT on the NOZ cell line, which represents a human carcinoma of the gallbladder and extrahepatic biliary tract

Summary

Introduction

Photodynamic therapy (PDT) for neoplasms has the following three components: a photosensitizer (PS), light, and oxygen [1]. In type II reactions, the PS molecule in the T1 state reacts directly with triplet oxygen via the transfer of energy to form singlet oxygen [3] Both superoxide anion radical and singlet oxygen are reactive oxygen species (ROS). We evaluated the relationship between mitochondrial ROS (mitROS) and HCP1 expression using rat gastric mucosal cells, RGM1, its cancer-like mutants, RGK1, obtained by treatment with carcinogenic chemicals, and manganese superoxide dismutase (MnSOD)-overexpressing RGK cells, RGK-MnSOD. These cells were previously established in our laboratory [12,13,14]. We evaluated whether (1) PLP accumulation is a cancer cell-specific phenomenon, (2) HCP1 is one of the PLP uptake transporters, and (3) PDT with PLP could be an efficient treatment for cholangiocarcinoma

Cell Culture

Cell Viability Assay

Localization of PLP in the Cells

PDT Treatment of Tumor-Bearing Mice

Findings

Conclusions