4.7 Article

Biodegradable biocompatible MgO/Eu nanodrug with Acid-Base conversion capacity for targeted lung cancer therapy

Journal

CHEMICAL ENGINEERING JOURNAL
Volume 446, Issue -, Pages -

Publisher

ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2022.136323

Keywords

Bioactive materials; Bioactive ceramic nanoparticles; Rare earth; MgO; Eu nanoparticle; Cancer therapy

Funding

  1. National Natural Science Foundation of China [52102306, 21971117]
  2. National Key R&D Program of China [2017YFA0208000]
  3. Basic Scientific Research in Central Universities [G2020KY0535]
  4. Foundation of Shaanxi Province Natural Science Basic Research Program [2022JQ-520, 2021JQ-095, 2020JQ-146]
  5. China Postdoctoral Science Foundation [2021M702609]
  6. Fundamental Research Funds for the Central Universities, Nankai University [63201071, ZB19500202]
  7. State Key Laboratory of Rare Earth Resource Utilization [RERU2019001]
  8. 111 Project from China [B18030]
  9. Beijing-Tianjin-Hebei Collaborative Innovation Project [63201058]
  10. Instrument Analysis Center of Xi?an Jiaotong University

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This study presents the application of biodegradable porous magnesium oxide nanoparticles with acid-base conversion ability in cancer therapy. These nanoparticles can rapidly convert to alkaline nanosheets under the acidic tumor microenvironment, allowing efficient uptake by cancer cells and suppression of tumor growth. This is the first example of responsive cancer therapy based on biodegradable single inorganic nanomaterials through chemical structure conversion mechanism.
Development of highly biocompatible biodegradable inorganic nanomaterials with targeted cancer therapy capacity is still a challenge. Herein, we report biodegradable porous magnesium oxide nanoparticles supporting europium atoms (MgO/Eu NPs) with proactive acid-base conversion ability for cancer therapy. MgO/Eu NPs could rapidly convert to alkaline nanosheet and biodegradation under acid tumor microenvironment, which enabled their significantly high lysosome uptake in lung cancer cell but not normal cells. The efficient uptake of NPs significantly activate the proapoptosis proteins, enhanced the generation of reactive oxygen species and mitochondria damage of cancer cells through inhibiting the lysosomal-autophagy process. MgO/Eu NPs are highly accumulated in tumor tissue, potently suppress tumor growth and biodegraded rapidly without adverse effects in vivo. This study demonstrates the first example in responsive cancer therapy based on biodegradable single inorganic nanomaterials through chemical structure conversion mechanism.

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