In Vitro Photodynamic Therapy with Chlorin e6 Leads to Apoptosis of Human Vascular Smooth Muscle Cells

Abstract

Percutaneous coronary intervention has become the most common and widely implemented method of heart revascularization. However, the development of restenosis remains the major limitation of this method. Photodynamic therapy (PDT) recently emerged as a new and promising method for the prevention of arterial restenosis. Here the efficacy of chlorin e6 in PDT was investigated in vitro using human vascular smooth muscle cells (TG/HA-VSMCs) as one of the cell types crucial in the development of restenosis. PDT-induced cell death was studied on many levels, including annexin V staining, measurement of the generation reactive oxygen species (ROS) and caspase-3 activity, and assessment of changes in mitochondrial membrane potential and fragmentation of DNA. Photosensitization of TG/HA-VSMCs with a 170 μM of chlorin e6 and subsequent illumination with the light of a 672-nm diode laser (2 J/cm2) resulted in the generation of ROS, a decrease in cell membrane polarization, caspase-3 activation, as well as DNA fragmentation. Interestingly, the latter two apoptotic events could not be observed in photosensitized and illuminated NIH3T3 fibroblasts, suggesting different outcomes of the model of PDT in various types of cells. The results obtained with human VSMCs show that chlorin e6 may be useful in the PDT of aerial restenosis, but its efficacy still needs to be established in an animal model.

Designing Multi‐Branched Gold Nanoechinus for NIR Light Activated Dual Modal Photodynamic and Photothermal Therapy in the Second Biological Window

“…The results in Figure S11 clearly reveals that the cellular deaths caused due to the phototoxicity of lipid‐coated Au NEs are much higher for HeLa cancerous cells when compared to non‐cancerous NIH‐3T3 fibroblast cells (for example, at 50 μg/mL, the percentages of cellular deaths for 915 nm at 37 °C for HeLa cells is ∼52% and NIH‐3T3 cells is ∼39%, whereas at 1064 nm irradiation, the percentages of cellular deaths for HeLa cells is ∼34% and NIH‐3T3 cells is ∼27%, respectively). The differences in the cellular viabilities of lipid‐coated Au NEs under photoirradiation conditions in cancerous and non‐cancerous cells are due to the variations in their abilities to undertake oxidative stress . Overall, both NmPTT‐ and NmPDT‐induced cellular deaths are responsible for the phototherapeutic destruction of solid tumors in mice upon 915 nm and 1064 nm light irradiation, with a larger fraction coming from the NmPDT effect.…”

Cellular Uptake and Photosensitizing Properties of Quantum Dot-Chlorin e<SUB>6</SUB> Complex: <I>In Vitro</I> Study

“…17 39 However the hydrophobic interaction between Ce 6 and QDs is weak and depends on surrounding molecules, therefore the stability of QD-Ce 6 complex must be considered. While Ce 6 molecule, a small amphiphilic compound, is preferentially taken up through the plasma membrane into inner lipid structures of the cell, [21][22][23] QDs tend to be taken up by endocytosis, 40-42 a form of membrane transport, where particles are transported to the endosomal vesicles. Since QDs are significantly larger than Ce 6 molecules, it is likely that internalization pathway of QDCe 6 complex is conditioned by the internalization of QDs.…”

“…18 19 Chlorins are able to generate singlet oxygen ( 1 O 2 ) with a high quantum yield 20 and to accumulate in cancer cells. [21][22][23] However Ce 6 is highly unstable under light exposure. 24 Its selectivity for malignant tissue is also questionable.…”

Anti-tumor activities of a novel chlorin derivative for photodynamic therapy in vitro and in vivo

“…[11][12][13][14] They are often selected because of their high singlet oxygen quantum yields and spectroscopic properties 15 : Characteristic absorption spectra with a Soret band at approximately 415 nm and a usually narrow but very strong Q-band around 650 nm, with a molar absorption coe±cient in the range of 10 5 M À1 cm À1 . Temopor¯n and mesotetahydroxyphenylchlorin have been used for esophageal cancer, head and neck cancer, early gastric cancer and gastrointestinal cancer super¯cial portion.…”