Enhanced Photodynamic Efficiency Achieved via a Dual-Targeted Strategy Based on Photosensitizer/Micelle Structure

Abstract

The applications of photodynamic therapy (PDT) are usually limited by photosensitizer's side effect and the singlet oxygen's short half-life. Herein, we demonstrate a dual-targeting (both cellular and subcellular targeting) strategy to enhance the PDT efficacy. A cationic porphyrin derivative (MitoTPP) was synthesized as the mitochondrion-targeting photosensitizer, and the dual-targeting PDT system was then fabricated by encapsulating MitoTPP into the acid-responsive and folic acid (FA)-modified polymer micelles. Under acidic pH, the micelles swell as a result of protonation of tertiary amines and disruption of the nucleobase pairing, thereby causing the release of the photosensitizer. Confocal microscope observation shows that the dual-targeting and micelle-based PDT system can preferably enter folate receptor (FR)-positive cancer cells, and upon cellular internalization, the MitoTPP molecules are released from the micelles and selectively accumulate in mitochondria. Under light irradiation, the singlet oxygen generated by the photosensitizer causes the oxidant damage to the mitochondrial and subsequently the apoptosis of the cells, as evidenced by the loss of mitochondrial membrane potential. Cell viability assays indicate that dual-targeting micelle-based systems exhibit enhanced cytotoxicity toward FR-positive cells. This study may provide a new approach for effectively enhancing the action of PDT systems.

Visible light photocatalytic disinfection of E. coli with TiO 2 –graphene nanocomposite sensitized with tetrakis(4-carboxyphenyl)porphyrin

“…Porphyrins absorb a broad range of the solar spectrum owing to their strong absorption band in both visible and near infrared regions [20]. Additionally, among the several classes of known photosensitizers, porphyrins are broadly used in antimicrobial photodynamic therapy [21,22].…”

Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer

“…For this reason, great effort has been focused on developing new mitochondria-specific PDT agents [13, 14]. Current mitochondria-targeting PSs are mostly based on cationic molecules, because the negative charges on mitochondria membranes allow for ionic interaction with these PSs.…”

Mitochondria‐Targeted Water‐Soluble Organic Nanoparticles of Chlorin Derivatives for Biocompatible Photodynamic Therapy

“…[17][18][19][20][21][22][23] Moreover, ionic polymers with polyethylene glycol, polymeric micells, and ionic surfactants provide better water solubility and stability. [24][25][26][27][28] However, these methods require an additional organic synthesis reaction, which is an uneconomical and a time-consuming process with low yield efficiency.…”