171749 20260603114407.0 doi 10.1002/adfm.202600080 sideral 149494 ART-2026-149494 eng Benaicha-Fernández, Amina Intrinsic Photoactive Star ZnPc–Poly(glutamate) Nanoplatforms for Multimodal Glioblastoma Therapy and Brain‐Targeted Delivery 2026 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. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/AEI/PID2021-126051OB-C41 info:eu-repo/grantAgreement/ES/DGA/T62-230R info:eu-repo/grantAgreement/ES/MCIU/PID2023-152459OB-I00 info:eu-repo/grantAgreement/ES/MICIU/PRTR-C17.I1 info:eu-repo/grantAgreement/ES/MINECO-RTICC-ISCIII-CIBERONC/CB22-12-0048 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Randelovic, Teodora (orcid)0000-0001-7232-7588 Armiñán, Ana Sebastián, Víctor Universidad de Zaragoza (orcid)0000-0002-6873-5244 Fuentes, Manuel Huck-Iriart, Cristián Masiá, Esther Carrascosa-Marco, Paula Juanes-Velasco, Pablo Ðordevic, Snežana Bayona, Clara Ochoa, Ignacio Universidad de Zaragoza (orcid)0000-0003-2410-5678 Medel, Maria Conejos-Sánchez, Inmaculada Vicent, María J. 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química (2026), e00080 [23 pp.] Adv. funct. mater. Advanced Functional Materials 1616-301X 5012225 http://zaguan.unizar.es/record/171749/files/texto_completo.pdf Versión publicada 2450917 http://zaguan.unizar.es/record/171749/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:171749 articulos driver 2026-06-03-11:04:33 ARTICLE