A Prospective Progress about Chemical and Biophysical Signatures of the Protein Corona in Nanomedicine

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Recently, a research team led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) was invited to publish a Perspective article in the journal of J Am Chem Soc (2022, 144, 21, 9184-9205).

Once the nanoparticles enter the organism, their surface will quickly adsorb protein molecules to form "nano-protein corona". The presence of protein corona will affect and regulate the behavior of the nanoparticles in the organism, their metabolic processes and ultimate fate in vivo, and then affect the biomedical function of nanopharmaceuticals. The formation of the protein corona is influenced by nanomaterials and their physicochemical properties, including size, structure, crystal form and type of surface modified molecules, electrical charge, chirality, etc. At the same time, these properties will affect the site of interaction between biomolecules and nanomaterials, molecular orientation, and biological activity. The study of nano-protein corona is crucial to guide the rational design and clinical translation of nanomedicines.

The research team has long been committed to the establishment of analytical methods for nano-protein corona and their chemical biological effects, including the chemical biological characteristics of nanoprotein corona, in vivo distribution and the transformation products. In recent years, they developed the characterization methods involving isotope labeling, synchrotron radiation scientific devices, spatial multi-omics methods and other highly sensitive and high-resolution in situ quantitative methods to reveal the adsorption law as well as chemical biological characteristics of nano-protein coronas (Nat Nanotechnol, 2021, 16, 708-716; Nat Nanotechnol, 2019, 14, 719-72; Nano Lett, 2021, 21, 6005-6013; Nano Lett, 2019, 19, 4692-4701; ACS Nano, 2020, 14, 5529?5542; J Am Chem Soc, 2013, 135, 17359-17368; PNAS, 2011, 108, 16968-16973, etc.). These studies provide a key and cutting-edge analytical tool for nano-biological effects, and provide new insights for in-depth understanding of the complex biological effects of nano-biological interfaces, which has greatly promoted the development of nano-biology.

In this perspective article, the authors deeply discuss the complex interplay between nanoparticles and their biological microenvironments, systematically summarize the chemical and biophysiological characteristics of nano-protein coronas, summarize the latest analytical techniques for determining the abundance, composition and transformation of protein coronas, elaborate nanoparticles across cell and paracellular uptake pathways modulated by the protein corona, and highlight the mechanism of different serum proteins mediating precise targeted delivery. By regulating the molecular composition and surface functionalization of nanoparticles (strategies such as coupling polymers with stealth properties and antibodies to the surface of nanoparticles) to prolong their blood circulation time and enhance tissue target ability. Finally, how to use the chemical properties of nano-protein coronas to guide the design of safe and effective nanomedicines is prospected, and the challenges in the study of the chemical and biological effects of the protein corona and many urgent problems to be solved are also proposed.

REN Jiayu from NCNST, Nicholas Andrikopoulos from Monash University in Australia, and Kelly Velonia from the University of Crete in Greece, are the co-first authors of this paper. Prof. CHEN Chunying from NCNST is the corresponding author. This series of research was supported by the National Key Research and Development Program, the National Natural Science Foundation of China Innovation Group, and the Strategic Priority Research Program of CAS.

The chemical identity of nanoparticles affect their protein corona properties, which in turn determine their biological identity and influence subsequent biological behavior (Image by CHEN Chunying et al)


Contact: CHEN Chunying

National Center for Nanoscience and Technology (NCNST)

E-mail: chenchy@nanoctr.cn


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