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Effects of microsize on the biocompatibility of UiO67 from protein-adsorption behavior, hemocompatibility, and
1School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, China.
Abstract:
The biocompatibility of metal-organic frameworks (MOFs) is necessary to humans but is far from being sufficiently addressed. This study focused on the effects of microsize on the biocompatibility of MOFs by selecting UiO67 with micron and submicron size as the MOFs models. Under the dose metric of surface area, the binding constant between UiO67 and human serum albumin (HSA) gradually increased with increased UiO67 size. Submicron UiO67 induced stronger conformational transformation and more greatly affected the protein surface hydrophobicity than micron UiO67. Micron UiO67 also inhibited the esterase-like activity of HSA through competitive inhibition mechanism, whereas submicron UiO67 inhibited it through noncompetitive inhibition mechanism. The size of UiO67 had little effect on hemocompatibility. A smaller size of UiO67, corresponded with a higher IC50 value for 293 T and LO2 cells, and the adsorption of HSA can effectively improve cytotoxicity. In vivo toxicity evaluations revealed that all UiO67 did not cause obvious distortion of organs, and they were metabolized primarily in the kidney. These results provided useful information about the toxicity of MOFs and experimental references for the development of MOFs-based engineering materials.
Insights
Metal-organic frameworks (MOFs) size impacts human serum albumin (HSA) interaction and cytotoxicity. Smaller MOFs exhibit higher toxicity but HSA adsorption mitigates this, with minimal in vivo organ distortion observed.
Area of Science:
- Materials Science
- Biomaterials Science
- Nanotechnology
Background:
- Biocompatibility of metal-organic frameworks (MOFs) is crucial for human applications but remains inadequately understood.
- Understanding how particle size influences MOF interactions with biological systems is essential for safe material development.
Purpose of the Study:
- To investigate the effect of microsize (micron vs. submicron) on the biocompatibility of UiO67 metal-organic frameworks.
- To elucidate the interaction mechanisms between UiO67 MOFs of different sizes and human serum albumin (HSA).
- To evaluate the cytotoxicity and in vivo toxicity of size-variant UiO67 MOFs.
Main Methods:
- Comparative analysis of micron and submicron UiO67 MOFs.
- Assessment of UiO67 binding affinity and conformational changes with HSA.
- Evaluation of HSA esterase-like activity inhibition by different sized UiO67.
- In vitro cytotoxicity assays (IC50) on 293T and LO2 cells.
- In vivo toxicity studies focusing on organ distortion and metabolism.
Main Results:
- UiO67 size positively correlated with HSA binding constants; submicron UiO67 induced greater protein conformational changes and hydrophobicity alterations.
- Micron UiO67 competitively inhibited HSA activity, while submicron UiO67 used a noncompetitive mechanism. Hemocompatibility was largely unaffected by size.
- Smaller UiO67 particles showed higher IC50 values, indicating increased cytotoxicity, which was mitigated by HSA adsorption. In vivo studies showed no significant organ damage, with primary metabolism in the kidneys.
Conclusions:
- MOF size significantly influences protein interactions, enzyme activity inhibition, and cytotoxicity.
- HSA adsorption can ameliorate the cytotoxicity of smaller MOFs, highlighting a potential protective mechanism.
- UiO67 MOFs demonstrate acceptable in vivo biocompatibility, primarily metabolized by the kidneys, providing valuable data for MOF-based material development.
