Acid-Degradable Hydrogen-Generating Metal-Organic Framework for Overcoming Cancer Resistance/Metastasis and Off-Target Side Effects.
Xianxian Yao, Danyang Chen, Bin Zhao, Binru Yang, Zhaokui Jin, Mingjian Fan, Geru Tao, Shucun Qin, Wuli Yang, Qianjun He · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
Research-use notice
Independent study record
Each H2HUBB study page organizes source-linked research details for educational use. Interpretation should remain proportional to the study design, population, controls, and limitations.
H2HUBB TAKEAWAY
In a laboratory model, mechanistically, released H₂ assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1-phenotype macrophages and consequently downregulating the expression of metastasis-related matrix metalloproteinase-2 (MMP-2) and can also downregulate the expressions of both P-glycoprotein (P-gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA. These findings come from a laboratory model and suggest molecular hydrogen's biological potential. Further research is needed to determine clinical relevance.
What the Researchers Tested
The study examined in vitro cell-culture laboratory experiment.
How Molecular Hydrogen Was Used
A new type of porphyrin-iron metal organic framework (Fe-MOF) nanocrystals is engineered here as acid-degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero-valence Fe atom. Fe-MOF nanocrystals exhibit excellent acid-responsive degradation for H₂ generation and simultaneous release of the loaded drug for combined hydrogen-chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off-target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H₂ assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1-phenotype macrophages and consequently downregulating the expression of metastasis-related matrix metalloproteinase-2 (MMP-2) and can also downregulate the expressions of both P-glycoprotein (P-gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA.
What Molecular Hydrogen Changed
A new type of porphyrin-iron metal organic framework (Fe-MOF) nanocrystals is engineered here as acid-degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero-valence Fe atom. Fe-MOF nanocrystals exhibit excellent acid-responsive degradation for H₂ generation and simultaneous release of the loaded drug for combined hydrogen-chemotherapy of cancer multidrug resistance (MDR) and metastasis and for local hydrogen eradication of the off-target induced toxic side effects of the drug to normal cells/tissues. Mechanistically, released H₂ assists chemotherapeutic drug to efficiently inhibit cancer metastasis by immunoactivating intratumoral M1-phenotype macrophages and consequently downregulating the expression of metastasis-related matrix metalloproteinase-2 (MMP-2) and can also downregulate the expressions of both P-glycoprotein (P-gp) protein and adenosine triphosphate (ATP) in MDR cancer cells to sensitize chemotherapeutic drug for enhanced damage to mitochondria and DNA.
H₂ Mechanisms / Biological Findings
The source material reviewed did not establish a specific molecular hydrogen mechanism for the reported findings.
Authors’ Conclusion
A distinct authors’ conclusion was not available in the source material reviewed by H2HUBB.