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In clinical applications, some biomedical nanomaterials are often introduced into blood tissue by intravenous injection, penetration, dissolution, and diffusion. Blood is a highly complex tissue, mainly composed of red blood cells, white blood cells, platelets and plasma. Among them, plasma is a complex body fluid, which contains more than 3700 different proteins. These nanomaterials will inevitably have some kind of connection or interaction with abundant plasma proteins (or other blood components) no matter which way. The interaction between nanomaterials and plasma proteins may change the structure, conformation and polarity of plasma proteins, and eventually lead to the exposure of new antigenic determinants and change the function of plasma proteins, resulting in the toxicity of nanomaterials in vitro or in vivo. A clear understanding of this issue will help guide the safety design of nanomaterials.
Nanomaterials in a blood associate with a range of proteins, organized into the protein "corona"
Function | Analytical Methods |
---|---|
Observation of the nanomaterials/protein complexes formation | Transmission electron microscopy (TEM) Atomic force microscopy (AFM) |
Binding affinity and ratio of nanomaterials interaction with protein | UV-vis spectroscopy (UV) Fluorescence spectroscopy Dynamic light scattering (DLS) |
Structure changes of nanomaterials-bound protein | Circular dichroism spectroscopy (CD) Fourier transform infrared spectroscopy (FT-IR) Raman spectroscopy Small-angle X-ray scattering (SAXS) Electron paramagnetic resonance (EPR) |
Isolation and separation of nanomaterials-bond proteins | Gel electrophoresis (GE) Capillary electrophoresis (CE) Gel permeation chromatography (GPC) High performance liquid chromatography (HPLC) |
Identification of nanomaterials-bound proteins | Mass spectrometry (MS) N-terminal microsequencing |
Kinetics of nanomaterials-proteins binding | Quartz crystal microbalance (QCM) Surface plasmon resonance (SPR) |
Thermodynamics of nanomaterials-protein binding | Differential scanning calorimetry (DSC) Isothermal titration calorimetry (ITC) |
Interaction test between polycation and plasma protein
Polycations are a kind of polymer materials with positive charge on the surface, such as polyethyleneimine, chitosan, polyamide-amine, etc., which can be used as gene delivery carriers. With the deepening of the research, it is found that these polycationic carriers generally have obvious cytotoxicity, which limits the production and commercialization of polycationic gene carriers. In addition, when polycation is used in vivo, it may also cause other toxicity, such as immunotoxicity and hemolytic toxicity.
Interaction test of polymer micelles with plasma proteins
Polymer micelles are supramolecular nanoparticles with core-shell structure formed by self-assembly of amphiphilic polymers in aqueous solution. In the targeted delivery of hydrophobic drugs, smart polymer micelles are an ideal drug carrier. The hydrophobic core of polymer micelles can provide loading space for hydrophobic drug molecules, increase the solubility of hydrophobic drugs, and prolong the circulation time of drugs in the body; on the other hand, the functional responsiveness of micelles can be used to achieve targeted drug release in a specific time and space. However, as a polymer micelle used in vivo, it is also inevitable to contact with plasma proteins and interact with each other.
Interaction test of drug (gene) / carrier composite nanoparticles and plasma proteins
In clinical application, when patients take medicine, it is not only the drug that enters the body, but also its carrier, that is, the drug (gene) / carrier composite nanoparticles enter the body. When these composite nanoparticles contact with plasma proteins, there may be three kinds of interactions between them: (1) the interaction between drugs and plasma proteins; (2) the interaction between carriers and plasma proteins; (3) the interaction between drug (gene) / carrier composite nanoparticles and plasma proteins.
Interaction test of other polymer nanomaterials and plasma proteins
There are many kinds of polymer nanomaterials, including not only polycations, micelles and composite nanoparticles, but also anionic polymer polyelectrolytes such as polyacrylic acid, neutral polymers such as polyvinyl alcohol and PEG, and polymer vesicles of various shapes. Although plasma proteins are generally negatively charged, there are still positively charged plasma proteins; at the same time, uneven charge distribution can also make plasma proteins locally positively charged. Therefore, anionic polymers may produce electrostatic interactions, hydrogen bonding interactions, and hydrophilic-hydrophobic interactions with plasma proteins.
As a professional third-party organization, Alfa Chemistry's professional capabilities are rooted in a long and successful history. With many years of testing experience, we can provide independent, fast-response, and cost-effective nanomaterial analysis services to help you shorten the time to market products, reduce risks, and increase the market value of products.
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