Intrinsic Photoactive Star ZnPc–Poly(glutamate) Nanoplatforms for Multimodal Glioblastoma Therapy and Brain‐Targeted Delivery
Benaicha-Fernández, Amina ; Randelovic, Teodora ; Armiñán, Ana ; Sebastián, Víctor (Universidad de Zaragoza) ; Fuentes, Manuel ; Huck-Iriart, Cristián ; Masiá, Esther ; Carrascosa-Marco, Paula ; Juanes-Velasco, Pablo ; Ðordevic, Snežana ; Bayona, Clara ; Ochoa, Ignacio (Universidad de Zaragoza) ; Medel, Maria ; Conejos-Sánchez, Inmaculada ; Vicent, María J.
Resumen: ABSTRACT
The design of polymeric systems with intrinsically integrated imaging and responsive functionalities represents a promising strategy to address the complexity of aggressive tumors such as glioblastoma multiforme (GBM). We report a class of star‐shaped zinc phthalocyanine–poly(L‐glutamic acid) (ZnPc‐PGA) nanocarriers in which the photoactive ZnPc core serves as a macroinitiator for the N‐carboxyanhydride ring‐opening polymerization, enabling control over chain length, architecture, and stoichiometry. ZnPc‐PGA nanocarriers exhibited near‐infrared absorption, enabling their implementation as imaging agents and photosensitizers for photodynamic therapy. Physicochemical characterization of ZnPc‐PGA nanocarriers revealed chain‐length‐ and concentration‐dependent supramolecular assembly. ZnPc‐PGA nanocarriers demonstrated lysosomal uptake/light‐activated cytotoxicity in GBM cells, while evaluation in the GBM‐on‐a‐chip platform confirmed oxygen‐dependent therapeutic outcomes. Proteomic profiling revealed a fibrinogen‐, cytoskeletal‐, and olfactory protein‐enriched corona, providing insight into potential biointerface interactions. Post‐polymerization conjugation of ZnPc‐PGA nanocarriers with paclitaxel facilitated multimodal therapy with enhanced efficacy in GBM cells, while integrating ZnPc‐PGA nanocarriers into a hyaluronic acid‐based hydrogel enabled intranasal delivery and resulted in brain accumulation. Overall, ZnPc‐PGA represents a modular nanoplatform and underscores the role of polymer architecture in dictating behavior in complex biological environments, with potential applicability in the design of multifunctional systems for challenging diseases such as GBM.
Idioma: Inglés
DOI: 10.1002/adfm.202600080
Año: 2026
Publicado en: Advanced Functional Materials (2026), e00080 [23 pp.]
ISSN: 1616-301X
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2021-126051OB-C41
Financiación: info:eu-repo/grantAgreement/ES/DGA/T62-230R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2023-152459OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICIU/PRTR-C17.I1
Financiación: info:eu-repo/grantAgreement/ES/MINECO-RTICC-ISCIII-CIBERONC/CB22-12-0048
Tipo y forma: Article (Published version)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material.
Exportado de SIDERAL (2026-06-03-11:04:33)
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The design of polymeric systems with intrinsically integrated imaging and responsive functionalities represents a promising strategy to address the complexity of aggressive tumors such as glioblastoma multiforme (GBM). We report a class of star‐shaped zinc phthalocyanine–poly(L‐glutamic acid) (ZnPc‐PGA) nanocarriers in which the photoactive ZnPc core serves as a macroinitiator for the N‐carboxyanhydride ring‐opening polymerization, enabling control over chain length, architecture, and stoichiometry. ZnPc‐PGA nanocarriers exhibited near‐infrared absorption, enabling their implementation as imaging agents and photosensitizers for photodynamic therapy. Physicochemical characterization of ZnPc‐PGA nanocarriers revealed chain‐length‐ and concentration‐dependent supramolecular assembly. ZnPc‐PGA nanocarriers demonstrated lysosomal uptake/light‐activated cytotoxicity in GBM cells, while evaluation in the GBM‐on‐a‐chip platform confirmed oxygen‐dependent therapeutic outcomes. Proteomic profiling revealed a fibrinogen‐, cytoskeletal‐, and olfactory protein‐enriched corona, providing insight into potential biointerface interactions. Post‐polymerization conjugation of ZnPc‐PGA nanocarriers with paclitaxel facilitated multimodal therapy with enhanced efficacy in GBM cells, while integrating ZnPc‐PGA nanocarriers into a hyaluronic acid‐based hydrogel enabled intranasal delivery and resulted in brain accumulation. Overall, ZnPc‐PGA represents a modular nanoplatform and underscores the role of polymer architecture in dictating behavior in complex biological environments, with potential applicability in the design of multifunctional systems for challenging diseases such as GBM.
Idioma: Inglés
DOI: 10.1002/adfm.202600080
Año: 2026
Publicado en: Advanced Functional Materials (2026), e00080 [23 pp.]
ISSN: 1616-301X
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2021-126051OB-C41
Financiación: info:eu-repo/grantAgreement/ES/DGA/T62-230R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2023-152459OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICIU/PRTR-C17.I1
Financiación: info:eu-repo/grantAgreement/ES/MINECO-RTICC-ISCIII-CIBERONC/CB22-12-0048
Tipo y forma: Article (Published version)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material. Exportado de SIDERAL (2026-06-03-11:04:33)
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Este artículo se encuentra en las siguientes colecciones:
Articles > Artículos por área > Ingeniería Química
Articles > Artículos por área > Histología
Record created 2026-06-03, last modified 2026-06-03