Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy
<b>Background:</b> Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylf...
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2025-05-01
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| author | Matías Daniel Caverzan Ana Belén Morales Vasconsuelo Laura Cerchia Rodrigo Emiliano Palacios Carlos Alberto Chesta Luis Exequiel Ibarra |
| author_facet | Matías Daniel Caverzan Ana Belén Morales Vasconsuelo Laura Cerchia Rodrigo Emiliano Palacios Carlos Alberto Chesta Luis Exequiel Ibarra |
| author_sort | Matías Daniel Caverzan |
| collection | DOAJ |
| description | <b>Background:</b> Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photodynamic 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. <b>Methods</b>: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemolysis assays were used to assess blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 h 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. <b>Results</b>: 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 administrations revealed no significant changes in body/organ weights, hematological parameters (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. <b>Conclusions</b>: Platinum porphyrin–doped F8BT CPNs exhibited minimal acute and subacute toxicity, 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. |
| format | Article |
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| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-d65063a7757b4e62ac1c7a216f2d3a0c2025-08-20T01:56:38ZengMDPI AGPharmaceutics1999-49232025-05-0117559310.3390/pharmaceutics17050593Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic TherapyMatías Daniel Caverzan0Ana Belén Morales Vasconsuelo1Laura Cerchia2Rodrigo Emiliano Palacios3Carlos Alberto Chesta4Luis Exequiel Ibarra5Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Río Cuarto X5800BIA, ArgentinaInstituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rio Cuarto X5800BIA, ArgentinaInstitute of Endotypes in Oncology, Metabolism and Immunology “Gaetano Salvatore”, National Research Council, 80131 Naples, ItalyInstituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Río Cuarto X5800BIA, ArgentinaInstituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Río Cuarto X5800BIA, ArgentinaInstituto de Biotecnología Ambiental y Salud (INBIAS), Universidad Nacional de Río Cuarto (UNRC) y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Rio Cuarto X5800BIA, Argentina<b>Background:</b> Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photodynamic 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. <b>Methods</b>: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemolysis assays were used to assess blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 h 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. <b>Results</b>: 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 administrations revealed no significant changes in body/organ weights, hematological parameters (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. <b>Conclusions</b>: Platinum porphyrin–doped F8BT CPNs exhibited minimal acute and subacute toxicity, 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.https://www.mdpi.com/1999-4923/17/5/593conjugated polymer nanoparticlesbiocompatibilitytoxicity evaluationsingle and repeated dose toxicityphotodynamic therapy |
| spellingShingle | Matías Daniel Caverzan Ana Belén Morales Vasconsuelo Laura Cerchia Rodrigo Emiliano Palacios Carlos Alberto Chesta Luis Exequiel Ibarra Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy Pharmaceutics conjugated polymer nanoparticles biocompatibility toxicity evaluation single and repeated dose toxicity photodynamic therapy |
| title | Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy |
| title_full | Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy |
| title_fullStr | Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy |
| title_full_unstemmed | Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy |
| title_short | Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy |
| title_sort | preclinical toxicological characterization of porphyrin doped conjugated polymer nanoparticles for photodynamic therapy |
| topic | conjugated polymer nanoparticles biocompatibility toxicity evaluation single and repeated dose toxicity photodynamic therapy |
| url | https://www.mdpi.com/1999-4923/17/5/593 |
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