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Clinical-Inspired Design of Self-Assembled Albumin-CeO2 Nanozymes for Oxygen-Self-Sufficient and Targeted

Mei Zhou1, Tingting Xu1, Shengnan Yuan2

  • 1Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, Nanjing, P. R. China.

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|December 27, 2025
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Summary
This summary is machine-generated.

Engineered nanozymes target triple-negative breast cancer (TNBC) by leveraging SPARC expression and modulating hypoxia. This approach enhances synergistic sonodynamic-chemotherapy, significantly suppressing tumor growth and offering a new treatment strategy.

Keywords:
nanozymesonodynamic therapytargeted drug deliverytriple‐negative breast cancertumor hypoxia

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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
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Area of Science:

  • Biomedical Engineering
  • Nanomedicine
  • Oncology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive, metastatic, and has limited treatment options.
  • TNBC tumors exhibit severe hypoxia and elevated secreted protein acidic and rich in cysteine (SPARC).
  • Hypoxia contributes to treatment resistance in TNBC.

Purpose of the Study:

  • To develop targeted nanozymes for synergistic sonodynamic-chemotherapy in TNBC.
  • To couple SPARC-mediated tumor targeting with hypoxia modulation.
  • To overcome treatment refractoriness in hypoxia-associated cancers.

Main Methods:

  • Engineered albumin-cerium oxide nanozymes (ACCD NPs) for targeted drug delivery (doxorubicin, DOX) and sonodynamic therapy (chlorin e6, Ce6).
  • Utilized SPARC-receptor interactions for selective albumin-mediated delivery.
  • Incorporated oxygen vacancy-engineered cerium oxide (CeO2) to decompose H2O2 and generate oxygen, alleviating tumor hypoxia.
  • Investigated in vitro and in vivo efficacy, including tumor accumulation, growth suppression, and molecular mechanism analysis.

Main Results:

  • ACCD NPs showed efficient targeted uptake and lysosome-responsive DOX release in vitro.
  • Ultrasound irradiation amplified reactive oxygen species production, enhancing synergistic cytotoxicity.
  • In vivo studies demonstrated 3.8-fold higher tumor accumulation, 84.9% TNBC growth suppression, and HIF-1α downregulation without systemic toxicity.
  • Mechanistic studies revealed autophagy and pyroptosis activation, oncogenic signaling suppression, and tumor suppressor gene upregulation.

Conclusions:

  • The developed nanoplatform effectively targets TNBC by addressing SPARC expression and tumor hypoxia.
  • ACCD NPs enable synergistic sonodynamic-chemotherapy, significantly inhibiting tumor progression.
  • This clinically informed strategy offers a versatile therapeutic paradigm for hypoxia-associated, treatment-refractory cancers.