Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and N-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of <50 mm3) and large (tumor volume of >50 mm3) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.

2‐deoxy‐D‐glucose augments photodynamic therapy induced mitochondrial caspase‐independent apoptosis and energy‐mediated autophagy

“…Tumor volumes and the body weight of the animals were measured every second day for 15 days after the start of treatment. The long (a) and short (b) diameters of the tumors were measured using slide calipers, and the mean tumor volume was calculated using the formula: ab 2 /2 . The volume inhibition ratio was calculated as follows: (1‐average tumor volume of treated group/average tumor volume of the control group) × 100%.…”

Endoscopic Probe for Ultrasound-Assisted Photodynamic Therapy of Deep-Lying Tissue

“…This scattering causes the energy loss and defocusing of the irradiated light. Due to this, the optimum depth of PDT is up to 10 mm [23], [24], and it is difficult to treat tumors larger than 10 mm in diameter [25]. The USassisted endoscopic PDT is performed by transmitting US and light simultaneously as shown in Fig.…”

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

“…Photodynamic therapy (PDT)-also called 'patient-specific cancer therapy', based on a therapeutic effect induced by a photosensitizer (PS), light, and oxygen-is a non-invasive cancer treatment with a low side-effect. [1][2][3][4][5][6] Photoirradiation activates the PS from the ground state (S 0 ) to the singlet state (S 1 ), followed by an intersystem crossing to reach the triplet state (T 1 ), which transfers electrons (Type I mechanism) and energy (Type II mechanism) to environmental oxygen, resulting in oxidative cell damage caused by the generation of reactive oxygen species (ROS; hydroxyl radicals, superoxide anions, and singlet oxygen ( 1 O 2 )). ROS are effective for destroying tumour cells through induced cell apoptosis and necrosis, microvasculature shutdown, and immune response.…”