X-ray liquid interface scattering results of structures between phospholipid (SOPC) and GOs. From J. Wu et al., Nat. Commun. 15, 8349 (2024). © 2024 Springer Nature Limited

The interface between nanomaterials and lipoproteins refers to the point of interaction where a nanomaterial comes into contact with a lipoprotein particle, leading to potential changes in both the nanomaterial’s properties and the lipoprotein’s structure and function. These changes are often influenced by such factors as surface chemistry, size, and charge of the nanomaterial, as well as the specific type of lipoprotein involved. This interaction is crucial in, for instance, understanding the biological effects of nanomaterials within the body, particularly when designing nanomedicines that aim to utilize lipoproteins as delivery vehicles. This study was carried out by a multination, multi-institution collaboration of researchers at a range of synchrotron light source facilities, including NSF’s ChemMatCARS at Sector 15 of the Argonne Advanced Photon Source, and several Chinese facilities. The study is particularly notable for highlighting the importance of structure analysis at the nano-biomolecule interface, and revealing the way nanomaterials’ surface properties infuence cellular lipid metabolism.

Experiments to determine the nanomaterials’ characteristics included: (1) x-ray refectivity experiments at the Liquid Surface/Interface X-ray Scattering facility of NSF’s ChemMat CARS employing a liquid surface refectometer to investigate the interaction of graphene oxides (GOs) with phospholipids; transmission microscope studies at the National Synchrotron Radiation Laboratory (China) for sample observation of lipid accumulation in THP-1 macrophages; x-ray absorption near edge structure measurements for the carbon element at the Shanghai Synchrotron Radiation Facility and the Beijing Synchrotron Radiation Facility (both China). In addition, the x-ray absorption near edge structure data were normalized using the IFEFFIT Athena software developed at the University of Chicago Center for Advanced Radiation Studies.

As shown by this study, surface chemistry is central to modulating intracellular lipid metabolism during interactions between nanomaterials and macrophages. Graphene oxides are revealed to be important in modeling hydrophobic carbon nanomaterials, showing the influence of surface chemistry on the formation of a specific lipoprotein corona,
resulting in changes to the structure and functions of lipoproteins, and thus regulating lipid metabolism at the molecular interface and cellular level.

By precision control of the oxidation degrees and surface functional groups of GOs, such as carboxyl and hydroxyl groups, distinct hydrophobicity/hydrophilicity can be achieved, meaning hydrophilic or hydrophobic GOs can enrich lipoproteins on their surface, resulting in different corona compositions of apolipoproteins in the presence of serum.

In sum, understanding the pathology of the effects of surface chemistry on nanomaterials provides a pathway to useful biomedical applications, particularly in the modulation of lipid metabolism.

See: Junguang Wu, Xuan Bai, Liang Yan, Didar Baimanov, Yalin Cong, Peiyu Quan, Rui Cai, Yong Guan, Wei Bu, Binhua Lin , JingWang, Shengtao Yu, Shijiao Li, Yu Chong, Yang Li, Guoqing Hu, Yuliang Zhao, Chunying Chen, and Liming Wang, “Selective regulation of macrophage lipid metabolism via nanomaterials’ surface chemistry,”
Nat. Commun. 15, 8349 (2024).

Author affiliations:

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences and New Cornerstone Science Laboratory, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China: Junguang Wu, Liang Yan, Didar Baimanov, Yalin Cong, Peiyu Quan, Rui Cai, Shengtao Yu, Shijiao Li, Yuliang Zhao, Chunying Chen, and Liming Wang

Sino-Danish College, University of Chinese Academy of Sciences: Junguang Wu

CAS-HKU Joint Laboratory of Metallomics on Health and Environment, Institute of High Energy Physics, Chinese Academy of Sciences: Junguang Wu, Didar Baimanov, Yalin Cong, Rui Cai, and Liming Wang

Department of Engineering Mechanics, State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University: Xuan Bai and Guoqing Hu

METiS Pharmaceuticals, Inc.: Xuan Bai

NSF’s ChemMatCARS, The University of Chicago, Peiyu Quan, Wei Bu, and Binhua Lin

National Synchrotron Radiation Laboratory, University of Science and Technology of China: Yong Guan

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University: Jing Wang

State Key Laboratory of Radiation Medicine and Radiation Protection, School of Radiation Medicine and Protection, Soochow University: Yu Chong

Laboratory of Inflammation and Vaccines, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences: Yang Li.

The GBA National Institute for Nanotechnology Innovation: Yuliang Zhao and Chunying Chen

Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences: Yuliang Zhao and Chunying Chen

This work was supported by the National Basic Research Program of China (2021YFA1200900 to C.C. and L.W. and 2020YFA0710702 to L.W.), the National Natural Science Foundation of China (32371469 to L.W., 31971322 to L.W.,
32350410425 to D.B., and 22388101 to C.C.), Science and Technology Innovation Project in IHEP (E25459U210 to L.W.), Directional Institutionalized Scientific Research Platform relies on Beijing Synchrotron Radiation Facility of the Chinese Academy of Sciences (E12982U813 to L.W.), Major Instrument Project of the National Natural Science Foundation of China (22027810 to C.C.), Beijing Natural Science Foundation (IS23023 to D.B.), the New Cornerstone Science Foundation (NCI202318) and China Postdoctoral Science Foundation (2023M742048 to D.B.). NSF’s
ChemMatCARS is supported by the Divisions of Chemistry (CHE) and Materials Research (DMR), National Science Foundation, under grant number NSF/CHE- 2335833.

For information on Liquid Surface/Interface Scattering program at NSF’s ChemMatCARS contact:

Wei Bu
(630) 252-0470
weibu@uchicago.edu