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A tumor microenvironment-responsive Zr-MOF nanosystem for co-delivering siHIF-1α and triptolide enhances photodynamic therapy in esophageal cancer by amplifying ROS generation and reversing hypoxia

2025-10Artigo científico Acesso aberto
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dc.contributor.authorLiu, Wenhan
dc.contributor.authorSun, Can
dc.contributor.authorDai, Yuhang
dc.contributor.authorWang, Huaiyong
dc.contributor.authorAshrafizadeh, Milad
dc.contributor.authorConde, João
dc.contributor.authorConde, João
dc.contributor.authorYang, Liyu
dc.contributor.authorHe, Wei
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionComprehensive Health Research Centre (CHRC) - pólo NMS
dc.contributor.pblElsevier BV
dc.date.accessioned2025-09-10T21:37:41Z
dc.date.available2025-09-10T21:37:41Z
dc.date.issued2025-10
dc.descriptionPublisher Copyright: © 2025 The Authors
dc.description.abstractIn addition to early diagnosis and on-time treatment, the adoption of new therapeutic strategies is of great significance for improving the clinical outcomes of patients with esophageal cancer. Although emerging therapies such as photothermal and photodynamic therapy (PDT) can precisely eliminate cancer cells and are alternative strategies to conventional treatments, hypoxia status of solid tumors have hindered their application. In recent years, nanoplatforms have been developed to address these limitations and improve the efficacy and safety of treatments. In addition, triptolide (TPL) and HIF-1α silencing may have potential value in cancer treatment by regulating oxidative stress. Inspired by these findings, we designed a cancer cell membrane-camouflaged porphyrin (photosensitizer) metal-organic framework (Zr-MOF@CM) for the co-delivery of TPL and HIF-1α small interfering RNA (siRNA) into tumor cells and tissues. The nanoparticles (TPL/siHIF-1α@Zr-MOF@CM) achieved targeted drug/gene/PDT synergistic therapy for esophageal cancer. This portable “all-in-one” drug delivery system exhibited good biocompatibility, sensitive pH-dependent drug release, and effective phagocytosis by esophageal cancer Kyse-30 cells. In addition, the nanoparticles produced large amounts of ROS and released drugs under near-infrared light (660 nm) irradiation, which significantly increased the apoptosis of esophageal cancer cells. Meanwhile, TPL and siHIF-1α released from the nanoparticles alleviated the hypoxic condition, further improving the PDT effect. In vivo experiments confirmed that TPL/siHIF-1α@Zr-MOF@CM maintained a long circulation time in tumor-bearing mice, specifically targeted the tumor site, and played a synergistic role with PDT to effectively reduce tumor growth. Importantly, TPL/siHIF-1α@Zr-MOF@CM exhibited a favorable biosafety profile in vitro and in vivo. This nanosystem is suitable for enhancing oxidative damage at tumor sites and is instructive for future design of PDT-dependent nanoplatforms.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent15880026
dc.identifier.doi10.1016/j.mtbio.2025.102183
dc.identifier.issn2590-0064
dc.identifier.otherPURE: 128516069
dc.identifier.otherPURE UUID: 9284dbb1-f26d-400a-89fc-860cd7ea0474
dc.identifier.otherScopus: 105013846345
dc.identifier.urihttp://hdl.handle.net/10362/187772
dc.identifier.urlhttps://www.scopus.com/pages/publications/105013846345
dc.language.isoeng
dc.peerreviewedyes
dc.subjectDrug and gene delivery
dc.subjectEsophageal cancer
dc.subjectMetal-organic framework
dc.subjectPhotodynamic therapy
dc.subjectReactive oxygen species
dc.subjectBiotechnology
dc.subjectBioengineering
dc.subjectBiomaterials
dc.subjectBiomedical Engineering
dc.subjectMolecular Biology
dc.subjectCell Biology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleA tumor microenvironment-responsive Zr-MOF nanosystem for co-delivering siHIF-1α and triptolide enhances photodynamic therapy in esophageal cancer by amplifying ROS generation and reversing hypoxiaen
dc.typejournal article
degois.publication.titleMaterials Today Bio
degois.publication.volume34
dspace.entity.typePublication
person.familyNameConde
person.givenNameJoão
person.identifier807432
person.identifier.ciencia-idA71C-B10E-255E
person.identifier.orcid0000-0001-8422-6792
person.identifier.ridF-2231-2011
person.identifier.scopus-author-id56992468300
rcaap.rightsopenAccess
relation.isAuthorOfPublication33ca4178-1b25-4b5e-ae16-b2500abe4c58
relation.isAuthorOfPublication.latestForDiscovery33ca4178-1b25-4b5e-ae16-b2500abe4c58

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