Targeting effective treatment to cutaneous Leishmaniasis: A preclinical investigation on photodynamic therapy mediated by the water-soluble Zn(II) porphyrin, ZnTnHex-2-PyP4+

Abstract

The current chemotherapy for cutaneous leishmaniasis (CL) is accompanied by side effects and drug resistance emergence, encouraging the proposal of new treatment approaches for this disease. ZnTnHex-2-PyP⁴⁺ (ZnP hexyl) is a water-soluble Zn(II) porphyrin that exhibits remarkable potential for photodynamic therapy (PDT). This study aimed to investigate the ZnP hexyl-PDT against CL in vivo. As far as we know, this is the first investigation with this Zn(II) porphyrin in an animal model. The influence of the number and time interval of sessions on photodynamic effects was also investigated. BALB/c mice infected with Leishmania amazonensis were divided in 4 groups (untreated control, 1, 2, or 3 PDT sessions). In PDT groups, animals received ZnP hexyl (5 μM, 0.17 μg, 30 μL per animal/session) and were irradiated with blue LED. Parasite burden was quantified by bioluminescence for up to 21 days. The infected paw thickness and nociceptive analyses were also assessed. In treated groups, parasite burden showed an over time decrease compared to the control, indicating ZnP hexyl-PDT efficiency, mainly after 3 sessions, achieving about 91% reduction. Overall, no differences in infected paw thickness and nociceptive sensibility were observed among the groups. Results also indicated the importance of tuning the time interval between sessions to enhance therapeutic outcomes and diminish adverse effects. Under the conditions studied, weekly PDT sessions were superior, as intervals ≤ 72-h led to a temporary increase in infected paw thickness and nociceptive sensibility at day 7. This study pointed out that ZnP hexyl-PDT holds promise as an ally for CL treatment.