Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy

Background: Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PS) of-fers promising cancer treatment potential but requires rigorous safety evaluation. Conju-gated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphy-rin-doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photo-dynamic efficiency but lack comprehensive preclinical toxicity data. This study aimed to evaluate the biocompatibility, biodistribution, and acute/subacute toxicity of these CPNs to establish their safety profile for clinical translation. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and char-acterized for colloidal stability in parenteral solutions. Hemolysis assays assessed blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 hours for 28 days) toxicity studies were conducted in BALB/c mice. Hematological, biochemical, histopathological, and biodistribution analyses (via ICP-MS) were performed to evaluate systemic and organ-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dextrose, with minimal aggregation. No hemolytic activity was observed at concentrations up to 50 mg/L. Single and repeated ad-ministrations revealed no significant changes in body/organ weights, hematological pa-rameters (except transient fibrinogen elevation), or liver/kidney function markers (ALT, AST, BUN, Cr). Histopathology showed preserved tissue architecture in major organs, with mild hepatocyte vacuolation at 30 days. Biodistribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclu-sions: Platinum porphyrin-doped F8BT CPNs exhibited minimal acute and subacute tox-icity, favorable biocompatibility, and no systemic adverse effects in murine models. These findings support their potential as safe PS candidates for PDT. However, chronic toxicity studies are warranted to address long-term organ accumulation and metabolic impacts. This preclinical evaluation provides a critical foundation for advancing CPNs toward clinical applications in oncology.