Photodynamic therapy of cottontail rabbit papillomavirus‐induced papillomas in a severe combined immunodeficient mouse xenograft system

Abstract

Objectives/Hypothesis To evaluate the efficacy of photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 for treating an animal model of recurrent respiratory papillomatosis (RRP). Methods Rabbit skin was grafted onto the dorsum of severe combined immunodeficient mice, two xenografts per animal. After the graft healed, it was inoculated with cottontail rabbit papillomavirus (CRPV). When papillomas developed, Pc 4 (0.6 or 1.0 mg/kg) was administered systemically, and 48 hours later, one papilloma of the two on each animal was exposed to 675-nm photoactivating light at either 100 or 150 J/cm2. In addition to the contralateral tumors, which received Pc 4 but no light, other controls included animals receiving light only or neither agent. Response was assessed by measuring papilloma size with a caliper. Some papillomas and residual skin were harvested for histological assessment. Results For the lower-dose PDT regimens, papilloma growth rates were not significantly different from the controls. In contrast, 13 of 15 papillomas receiving the higher Pc 4 dose (1.0 mg/kg) and the higher light fluence (150 J/cm2) regressed completely and did not regrow within the observation period of up to 79 days. The response of these papillomas was significantly different from the controls (P < .001). Histological analysis confirmed the absence of residual tumor following complete response and replacement with near-normal epithelium. Conclusions Pc 4-PDT is highly effective in treating virally induced (CRPV) papillomas in a murine model of RRP, and thus warrants further study as a treatment for HPV-induced papillomas.

Photo-oxidation of cardiolipin and cytochrome c with bilayer-embedded Pc 4

“…As an exogenous photosensitizer, Pc 4 has shown excellent treatment response in several different tumor models, including human tumor xenografts in immunocompromised mice [19-25], and is currently in a Phase I human clinical trial of PDT for the treatment of cutaneous tumors. In PDT, Pc 4 localizes in mitochondrial and endoplasmic reticulum/Golgi membranes [26] and induces apoptosis in many types of cells and tumors [27].…”

Photodynamic Therapy of Infectious Disease Mediated by Functionalized Fullerenes

“…These groups not only allow fullerenes to be effectively administered to a site of infection in vivo but also have demonstrated a notable increase in production of singlet oxygen species, hydroxyl radicals, and superoxide anion, making these particular fullerenes more effective PS. Another result of the addition of these groups is the functionalized fullerene being given multiple overall positive charges, which, as previously mentioned, can result in higher antimicrobial selectivity as well as improved uptake in Gram-negative cells Li et al, 2014).…”

“…Recurrence of these symptoms can be indicative of life-threatening conditions (Lieder et al, 2014). Lee et al (2010) examined the use of PDT with a phthalocyanine PS for treating mice grafted with cottontail rabbit skin and then infected with cottontail rabbit papillomavirus; 0.6 or 1.0 mg/kg of the PS were applied, along with 100 or 150 J/cm 2 of 675 nm light. At lower doses, this treatment proved to be ineffective with little regression of the papilloma; however, at 1.0 mg/kg and 150 J/cm 2 of light, there was "complete regression" of the papilloma at the site of infection with a significant difference in the controls (P value ,0.001).…”

Recurrent Respiratory Papillomatosis

“…In the case of RRP, the PDT may provide benefit by altering the immune response, making it more sensitive to even low concentrations of viral proteins. 131,132 Currently, there are some discrepancies concerning the benefit of PDT, with some studies showing decreased papilloma growth and potential long-term effects, whereas others show limited benefits. 133–135 PDT remains an area of future study to better understand its mechanism of action as well as to evaluate its benefit as adjuvant therapy.…”