Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

Abstract

We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice.

Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

“…Redaporfin presented in Figure 9 is a fully synthetic bacteriochlorin especially designed to combine the spectroscopic properties of bacteriochlorins with their photostability [53]. It interacts with molecular oxygen through type I and II mechanisms, which makes it highly effective in the treatment of a variety of cancer cells and tumors [5,[98][99][100]. Redaporfin is a bacteriochlorin, not a metallobacteriochlorin, but it is included in Table 3 to allow for a direct comparison with the photophysical and photochemical properties of the recently developed metallobacteriochlorins.…”

“…The insult mediated by oxidative stress at the targeted tissue triggers a complex multifactorial response engaging host defense mechanisms associated with the inflammatory process that participate in the eradication of the treated tumor and involve many elements of the innate and adaptive immune systems [5,21,22,28,274,275]. During photodynamic action, neutrophils are among the first cells recruited to the illuminated area [276].…”

“…Both aspects are essential for photodynamic therapy (PDT). PDT has emerged as a relatively non-invasive and innovative treatment modality [1][2][3][5][6][7][8] being applied mainly in the fields of oncology [1][2][3][5][6][7], ophthalmology [9][10][11][12] and microbiology [13]. PDT requires three separately non-toxic elements: a photochemically active drug (photosensitizer; PS), light and molecular oxygen dissolved in the tissue [1][2][3], which in combination lead to destruction of the target tissue.…”

Mechanistic studies on versatile metal-assisted hydrogen peroxide activation processes for biomedical and environmental incentives

“…It is an example of how the dynamics of the interaction between light, a photosensitizer and oxygen can be tuned to increase therapeutic efficacy. The fact that redaporfin interacts with molecular oxygen both through type I and type II photoreactions makes it versatile in the treatment of a variety of cancer cells and tumors, such as melanoma [233,234,242], lung adenocarcinoma [230,232] and colon carcinoma [275][276][277]. It is currently in phase II clinical trials for head and neck tumors.…”

Effects of arginine–glycine–aspartic acid peptide-conjugated quantum dots-induced photodynamic therapy on pancreatic carcinoma in vivo

“…[41][42][43] Most of the photosensitizers were distributed around the body and could induce injures to normal tissues. [44][45][46][47] Those results should be attributed (at least in part) to the conventional intravenous mode of injection. In this way, more photosensitizers are used, but fewer work in the treatment.…”