Health & Environmental Research Online (HERO)


Print Feedback Export to File
7190780 
Journal Article 
Enhanced photodynamic efficiency achieved via a dual-targeted strategy based on photosensitizer/micelle structure 
Xu, J; Zeng, F; Wu, H; Hu, C; Wu, S; , 
2014 
Yes 
Biomacromolecules
ISSN: 1525-7797 
AMER CHEMICAL SOC 
WASHINGTON 
4249-4259 
English 
25329523 
WOS:000344721400039 
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.