ArticleJournal of nanobiotechnology2021
Atovaquone-HSA nano-drugs enhance the efficacy of PD-1 blockade immunotherapy by alleviating hypoxic tumor microenvironment.
Article in Journal of nanobiotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 39 citations in OpenAlex.
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- Emerging Nanoplatforms are Effective Against Tumor Hypoxia.International journal of nanomedicine · 2026Review
- Metabolic rewiring of the tumor microenvironment: therapeutic intervention of multi-pathway adaptations to impede cancer metastasis.Frontiers in molecular biosciences · 2026Review
- Binding and transport functions of human serum albumin and its clinical implications in liver disease: a narrative review.Translational gastroenterology and hepatology · 2026Review
- Recent advances in albumin-based nanoparticle drug delivery systems for intestinal disease treatment.International journal of pharmaceutics: X · 2025Review
- Targeting DDOST improves the efficacy of lenvatinib and immunotherapy in hepatocellular carcinoma.Experimental & molecular medicine · 2025Article
- Enhancing radiotherapy-induced anti-tumor immunity via nanoparticle-mediated STING agonist synergy.Molecular cancer · 2025Review
- Tumor microenvironment-responsive precise delivery nanocarrier potentiating synchronous radionuclide therapy and chemotherapy against cancer.Journal of nanobiotechnology · 2025Article
- Mitochondria-targeted strategies in tumor immunity.Frontiers in immunology · 2025Review
- Targeting Tumor Hypoxia with Nanoparticle-Based Therapies: Challenges, Opportunities, and Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Engineering tumor-oxygenated nanomaterials: advancing photodynamic therapy for cancer treatment.Frontiers in bioengineering and biotechnology · 2024Review
- Disulfiram/Cu Kills and SensitizesInternational journal of molecular sciences · 2023Article
- Advances in tumor immunomodulation based on nanodrug delivery systems.Frontiers in immunology · 2023Review
- Improving the synergistic combination of programmed death-1/programmed death ligand-1 blockade and radiotherapy by targeting the hypoxic tumour microenvironment.Journal of medical imaging and radiation oncology · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHypoxia is inherent character of most solid malignancies, leading to the failure of chemotherapy, radiotherapy and immunotherapy. Atovaquone, an anti-malaria drug, can alleviate tumor hypoxia by inhibiting mitochondrial complex III activity. The present study exploits atovaquone/albumin nanoparticles to improve bioavailability and tumor targeting of atovaquone, enhancing the efficacy of anti-PD-1 therapy by normalizing tumor hypoxia.
methodsWe prepared atovaquone-loaded human serum albumin (HSA) nanoparticles stabilized by intramolecular disulfide bonds, termed HSA-ATO NPs. The average size and zeta potential of HSA-ATO NPs were measured by particle size analyzer. The morphology of HSA-ATO NPs was characterized by transmission electron microscope (TEM). The bioavailability and safety of HSA-ATO NPs were assessed by animal experiments. Flow cytometry and ELISA assays were used to evaluate tumor immune microenvironment.
resultsOur data first verified that atovaquone effectively alleviated tumor hypoxia by inhibiting mitochondrial activity both in vitro and in vivo, and successfully encapsulated atovaquone in vesicle with albumin, forming HSA-ATO NPs of approximately 164 nm in diameter. We then demonstrated that the HSA-ATO NPs possessed excellent bioavailability, tumor targeting and a highly favorable biosafety profile. When combined with anti-PD-1 antibody, we observed that HSA-ATO NPs strongly enhanced the response of mice bearing tumor xenografts to immunotherapy. Mechanistically, HSA-ATO NPs promoted intratumoral CD8
conclusionsOur data provide strong evidences showing that HSA-ATO NPs can serve as safe and effective nano-drugs to enhance cancer immunotherapy by alleviating hypoxic tumor microenvironment.
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