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

Autores
Caverzan, Matias Daniel; Morales Vasconsuelo, Ana Belen; Cerchia, Laura; Palacios, Rodrigo Emiliano; Chesta, Carlos Alberto; Ibarra, Luis Exequiel
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Photodynamic therapy (PDT) utilizing nano-based photosensitiz-ers (PS) offers promising cancer treatment potential but requires rigorous safety evalua-tion. 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. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemoly-sis 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 bio-distribution analyses (via ICP-MS) were performed to evaluate systemic and or-gan-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dex-trose, 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. Biodis-tribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: 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 accu-mulation and metabolic impacts. This preclinical evaluation provides a critical founda-tion for advancing CPNs toward clinical applications in oncology.
Fil: Caverzan, Matias Daniel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina
Fil: Morales Vasconsuelo, Ana Belen. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Cerchia, Laura. Consiglio Nazionale delle Ricerche; Italia
Fil: Palacios, Rodrigo Emiliano. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina
Fil: Chesta, Carlos Alberto. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina
Fil: Ibarra, Luis Exequiel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Materia
conjugated polymer nanoparticles
biocompatibility
toxicity evaluation
single and repeated dose toxicity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/273749
Acceder
id CONICETDig_7369bac29cb68173236d6ed6f5dd4983
oai_identifier_str oai:ri.conicet.gov.ar:11336/273749
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic TherapyCaverzan, Matias DanielMorales Vasconsuelo, Ana BelenCerchia, LauraPalacios, Rodrigo EmilianoChesta, Carlos AlbertoIbarra, Luis Exequielconjugated polymer nanoparticlesbiocompatibilitytoxicity evaluationsingle and repeated dose toxicityhttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2Background: Photodynamic therapy (PDT) utilizing nano-based photosensitiz-ers (PS) offers promising cancer treatment potential but requires rigorous safety evalua-tion. 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. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemoly-sis 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 bio-distribution analyses (via ICP-MS) were performed to evaluate systemic and or-gan-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dex-trose, 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. Biodis-tribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: 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 accu-mulation and metabolic impacts. This preclinical evaluation provides a critical founda-tion for advancing CPNs toward clinical applications in oncology.Fil: Caverzan, Matias Daniel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; ArgentinaFil: Morales Vasconsuelo, Ana Belen. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Cerchia, Laura. Consiglio Nazionale delle Ricerche; ItaliaFil: Palacios, Rodrigo Emiliano. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; ArgentinaFil: Chesta, Carlos Alberto. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; ArgentinaFil: Ibarra, Luis Exequiel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaMDPI2025-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/273749Caverzan, Matias Daniel; Morales Vasconsuelo, Ana Belen; Cerchia, Laura; Palacios, Rodrigo Emiliano; Chesta, Carlos Alberto; et al.; Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy; MDPI; Pharmaceutics; 17; 5; 4-2025; 1-241999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/17/5/593info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17050593info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:11:52Zoai:ri.conicet.gov.ar:11336/273749instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:11:52.37CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy
title Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy
spellingShingle Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy
Caverzan, Matias Daniel
conjugated polymer nanoparticles
biocompatibility
toxicity evaluation
single and repeated dose toxicity
title_short 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_sort Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy
dc.creator.none.fl_str_mv Caverzan, Matias Daniel
Morales Vasconsuelo, Ana Belen
Cerchia, Laura
Palacios, Rodrigo Emiliano
Chesta, Carlos Alberto
Ibarra, Luis Exequiel
author Caverzan, Matias Daniel
author_facet Caverzan, Matias Daniel
Morales Vasconsuelo, Ana Belen
Cerchia, Laura
Palacios, Rodrigo Emiliano
Chesta, Carlos Alberto
Ibarra, Luis Exequiel
author_role author
author2 Morales Vasconsuelo, Ana Belen
Cerchia, Laura
Palacios, Rodrigo Emiliano
Chesta, Carlos Alberto
Ibarra, Luis Exequiel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv conjugated polymer nanoparticles
biocompatibility
toxicity evaluation
single and repeated dose toxicity
topic conjugated polymer nanoparticles
biocompatibility
toxicity evaluation
single and repeated dose toxicity
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Background: Photodynamic therapy (PDT) utilizing nano-based photosensitiz-ers (PS) offers promising cancer treatment potential but requires rigorous safety evalua-tion. 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. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemoly-sis 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 bio-distribution analyses (via ICP-MS) were performed to evaluate systemic and or-gan-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dex-trose, 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. Biodis-tribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: 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 accu-mulation and metabolic impacts. This preclinical evaluation provides a critical founda-tion for advancing CPNs toward clinical applications in oncology.
Fil: Caverzan, Matias Daniel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina
Fil: Morales Vasconsuelo, Ana Belen. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
Fil: Cerchia, Laura. Consiglio Nazionale delle Ricerche; Italia
Fil: Palacios, Rodrigo Emiliano. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina
Fil: Chesta, Carlos Alberto. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina
Fil: Ibarra, Luis Exequiel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina
description Background: Photodynamic therapy (PDT) utilizing nano-based photosensitiz-ers (PS) offers promising cancer treatment potential but requires rigorous safety evalua-tion. 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. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemoly-sis 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 bio-distribution analyses (via ICP-MS) were performed to evaluate systemic and or-gan-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dex-trose, 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. Biodis-tribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: 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 accu-mulation and metabolic impacts. This preclinical evaluation provides a critical founda-tion for advancing CPNs toward clinical applications in oncology.
publishDate 2025
dc.date.none.fl_str_mv 2025-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/273749
Caverzan, Matias Daniel; Morales Vasconsuelo, Ana Belen; Cerchia, Laura; Palacios, Rodrigo Emiliano; Chesta, Carlos Alberto; et al.; Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy; MDPI; Pharmaceutics; 17; 5; 4-2025; 1-24
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/273749
identifier_str_mv Caverzan, Matias Daniel; Morales Vasconsuelo, Ana Belen; Cerchia, Laura; Palacios, Rodrigo Emiliano; Chesta, Carlos Alberto; et al.; Preclinical Toxicological Characterization of Porphyrin-Doped Conjugated Polymer Nanoparticles for Photodynamic Therapy; MDPI; Pharmaceutics; 17; 5; 4-2025; 1-24
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics17050593
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rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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application/pdf
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dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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