Abstract 3466: Mitochondrial targeting photosensitizer-lipophilic cation conjugates for photodynamic therapy

Abstract Mitochondrion of a living cell plays a pivotal role in apoptosis. Targeting the mitochondria of cancer cell for the induction of apoptosis in photodynamic therapy (PDT) has gained importance. Cancer cells have higher plasma and mitochondrial membrane potential compared to normal cells, consequently delocalized lipophilic cations (DLCs) tend to accumulate more in them than in normal cells. In PDT photosensitizers can be specifically delivered to the mitochondria of cancerous cell by conjugating them with DLCs. Three conjugates: CMP-TPP (a porphyrin-triphenyl phosphene monocation conjugate) and CMP-(TPP)2 (a porphyrin- triphenyl phosphene dication conjugate), CMP-Rh (a porphyrin -rhodamine monocation conjugate) were synthesized as mitochondria targeting photosensitizers. The conjugates were synthesized by conjugating a core modified porphyrin (CMP-TPP) to either 1 or 2 triphenyl phosphene (TPP) molecules or rhodamine B (Rh B) respectively via a saturated hydrocarbon linker. To evaluate the efficiency of the conjugates, the photophysical properties like fluorescence resonance energy transfer (FRET in CMP-Rh) and singlet oxygen generation was compared to that of the unconjugated CMP. Potent in vitro photodynamic activity was observed in Colon 26 cells upon treatment with CMP conjugates and exposure to 690 nm diode laser light source (5.6 mW/cm2 for 30 min, 10.8 J/cm2). No significant darktotoxicity was observed in cells treated up to 5 μM of the conjugates. The conjugates showed approximately 12-14 times higher uptake in Colon 26 cells compared to unconjugated porphyrin. Further, sub-cellular localization, comparison of preferential uptake by cancerous cells versus normal cells, in vivo bio-distribution, PDT in BALB/c mice will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3466. doi:1538-7445.AM2012-3466