ArticleACS biomaterials science & engineering2025
Oxygen-Releasing Nanodroplets Relieve Intratumoral Hypoxia and Potentiate Photodynamic Therapy in 3D Head and Neck Cancer Spheroids.
Article in ACS biomaterials science & engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Mesoscopic Fluorescence Imaging of Light-Triggered Chemotherapeutic Release in Cancer Spheroid Models.Pharmaceutics · 2026Article
- Hypoxia-induced drug-resistance bias 3D cancer spheroid drug screens.APL bioengineering · 2026Article
- Oxygen-releasing scaffolds in tissue engineering: design strategies, fabrication and regenerative applications.Regenerative biomaterials · 2026Review
- Label-Free Hemodynamic Mapping via Ultrafast Power Doppler-Enhanced Photoacoustic Imaging reveals early therapy-induced functional changes in the tumor.bioRxiv : the preprint server for biology · 2025Article
- Linking hypoxia-inducible factor (HIF)-1α and HIF-2α expression in head and neck cancer.Bioinformation · 2025Article
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Abstract
Hypoxia in solid tumors, including head and neck cancer (HNC), contributes to treatment resistance, aggressive tumor phenotypes, and poorer clinical outcomes. Perfluorocarbon nanodroplets have emerged as promising drugs to alleviate tumor hypoxia. These versatile nanocarriers can also encapsulate and deliver various therapeutic agents, offering a multifunctional approach to cancer treatment. However, a detailed characterization of hypoxia alleviation, particularly the duration of hypoxia treatment drug residence, has not been thoroughly investigated. In this study, we developed and characterized perfluoropentane nanodroplets (PFP NDs) for the codelivery of oxygen and the photoactivatable drug benzoporphyrin derivative (BPD) to hypoxic HNC spheroids. The PFP NDs exhibited excellent stability, efficient oxygen loading/release, and biocompatibility. Using 3D multicellular tumor spheroids of FaDu and SCC9 HNC cells, we investigated the spatiotemporal dynamics of hypoxia within these spheroids and the ability of oxygenated PFP NDs to alleviate hypoxia. Our results showed that oxygen-loaded PFP NDs effectively penetrated the core of tumor spheroids, significantly reducing hypoxia, as evidenced by the downregulation of hypoxia-inducible factors HIF-1α and HIF-2α. Importantly, we demonstrated sustained hypoxia alleviation for up to 3 h post-treatment with PFP NDs. BPD-loaded PFP NDs successfully delivered the photosensitizer into the spheroid core in a time-dependent manner. Furthermore, we evaluated the efficacy of oxygen-dependent treatment modality, namely, photodynamic therapy (PDT) with BPD and oxygen-loaded PFP NDs compared to free BPD. The NDs formulation exhibited superior PDT outcomes, which were attributed to improved oxygen availability during the treatment. This study provides comprehensive evidence for the potential of PFP NDs as a codelivery platform to overcome hypoxia-mediated treatment resistance and enhance PDT efficacy in HNC. Our findings pave the way for further investigation of this promising approach in more complex
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