DH‐I‐180‐3‐Mediated Photodynamic Therapy: Biodistribution and Tumor Vascular Damage

Abstract

An important goal of photodynamic therapy (PDT) for treatment of various cancers is to shorten PDT-performing time and simultaneously enhance PDT efficacy. Here, we investigated the nontumor tissue distribution of and the tumor vascular damage caused by a new photosensitizer, DH-I-180-3, in mice with implanted EMT6 mammary tumor cells. In addition, we performed cell-based assays to evaluate the basic antitumor effect of DH-I-180-3/PDT in EMT6 cells. After administration of PDT, the type of cell death was characterized to be apoptosis, and a change in the mitochondrial membrane potential was also observed within minutes. On the other hand, tumor growth was remarkably retarded in vivo in mice that received DH-I-180-3/PDT, compared with mice in the control group, which were exposed to light irradiation alone. Finally, tumors in some mice nearly healed. The antitumor drug reached a maximum concentration approximately 3 h after administration. However, PDT was most effective when there was substantial accumulation of DH-I-180-3 in the tumor vasculature and in healthy tissue. The histological demonstration provided further evidence of tumor vascular damage. On the basis of these findings, we suggest that PDT with the photosensitizer DH-I-180-3 induces vascular damage with blood vessel shutdown, in addition to direct killing of tumor cells, in mice.

Photophysical Properties of Pheophorbide-a Derivatives and Their Photodynamic Therapeutic Effects on a Tumor Cell LineIn Vitro

“…For evaluation of cell uptake efficiency of photosensitizer, mean fluorescence intensity (MFI) of photosensitizer which was loaded to the cell was measured [20]. The EMT6 cells (1 × 10 6 in a 35 mm tissue culture dish) were incubated with 1.5 mL of DMEM with photosensitizers (0.1 g/mL) for 1 hour at 37 ∘ C. These experiments were performed at the concentration range of PaDs where the nontoxicity was confirmed from previous reports [21,22]. After incubation with photosensitizers, the cells were harvested from 35 mm tissue culture dish.…”

“…After incubation, the cells were exposed to light for PDT. Then, the cells were further incubated at 37 ∘ C for 24 hours in a dark humidified incubator [21]. After the incubation, the cells were harvested from the 35 mm tissue culture dish and 100 L of MTT solution (1 mg/mL) was added to the cell pellets.…”

Sonodynamic therapy inhibits angiogenesis and tumor growth in a xenograft mouse model

“…SDT is usually thought to maximize its therapeutic effect on tumors and minimize side effects on the surrounding healthy tissues when the sonosensitizer ratio of tumor to normal tissue is maximal [8,11]. However, in recent years, increasing evidence in photodynamic therapy (PDT) accumulated suggests that plasma concentration (which reflects endothelial cell exposure) correlated better with the therapeutic effect than tumor concentration [38][39][40][41][42]. In this study, we chose 4 h as our DUI.…”

Study of efficiency of the modular nanotransporter for targeted delivery of photosensitizers to melanoma cell nuclei in vivo

“…It is worth mentioning that PDT of pigmented melanoma is challenging, due to the presence of melanin, which determines its pigmentation and absorbs light, thereby hampering light penetration into deeper layers of tissue [5]. However, the pronounced effect of MNTs on melanoma cells in vitro [4, 6] allowed us to assume that the small amounts of light penetrating the tumor may be sufficient for the manifestation of the effect of a photosensitizer delivered by MNT into the nucleus, the most sensitive compartment.…”