Bio-Corona: The Dark Side Of Nanomaterials And Nanoparticles

The Nanotoxicity of Bio-Corona Complexes

 
 https://www.ncbi.nlm.nih.gov/pubmed/29206030

https://www.ncbi.nlm.nih.gov/pubmed/29206030

 

If you asked me what is my least favorite beer, I would tell you it's for sure bio-corona.

All jokes aside, the way that nanoparticles form complexes with our body and can blindly pass the immune system is a big industrial-age problem we must face and it seems to be worse for those who already have excessive oxidative stress.

Contents:

  1. TLDR
  2. What Makes Bio-Corona?
  3. Examples Of Bio-Corona
  4. Benefits Of Bio-Corona
  5. Downsides To Bio-Corona
  6. What To Do About Bio-Corona?
  7. Mechanism Of Action

TLDR

Too Long Didn't Read (TLDR):

  • Biomolecules that bind a nanoparticle's surface are referred to as biocorona R
  • Biocorona can directly shift the immune system to an acute or chronic inflammatory state, or fully bypass the immune system and cause oxidative stress
  • There are many different types of nanoparticle structures which makes it difficult to tell what the biocorona complex will do inside the body
  • Avoiding exposure to nanoparticles/materials seems to be the first step to protection

What Makes Bio-Corona?

 
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875931/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875931/

 

    Throughout evolution, we have been exposed to food and environmental particles, a myriad of them being in the nanoparticle ranges, but the rise of the industrial revolution has significantly increased our exposure to nanoparticles (NP). R

    When nanoparticles are placed in any biological environment their surface becomes coated with a variety of biomolecules forming a biocorona (called the NP–protein corona complex). R

    Biocorona usually either form a soft corona (loose) or hard corona (tight). R

     
     https://www.sciencedirect.com/science/article/pii/S0041008X15301368

    https://www.sciencedirect.com/science/article/pii/S0041008X15301368

     

    Biocorona's action in the body are somewhat unpredictable at this time in research.

    Since their effects are based on where they act in the body and what NPs they are bound to,  bio-corona can either enhance or inhibit a certain cellular function/response. R

    Read all about nanoparticles, nanomaterials, and ultrafine particles here (unfinished link). 

    Examples Of Bio-Corona

    Bio-Corona can be formed when NP bind to certain biomolecules (proteins, membranes, cells, DNA and organelles) with the most prominently studied being: R

    • ECM constituents and receptors R
    • Fibrinogen R
    • Fungi R
    • Heparin R
    • Heparan Sulfate R
    • Human Serum Albumin (HSA) R
    • Immunoglobulin (IgG) R
    • Metals (such as silver, gold, titanium) R

    Benefits Of Bio-Corona

    1. Improves Nanoparticle Drug Delivery

    Nanotechnology is a prominent new area of research for delivering drugs to cells by bypassing certain systems in the body. R

    Bio-corona may extend the half-life of the NPs in systemic circulation. R

    Downsides To Bio-Corona

    1. Alters Extracellular Matrix Signaling

     
     https://www.ncbi.nlm.nih.gov/pubmed/26686425

    https://www.ncbi.nlm.nih.gov/pubmed/26686425

     

    The Extracellular Matrix (ECM) is the area outside the cell that provides structural and biochemical support to the surrounding cells. R

    Bio-corona can induce alterations in ECM interacting with cell surface receptors, growth factors and cytokines, leading to numerous signaling cascades which are closely related to cell behavior. R R R

    2. Causes Inflammation And Imbalances In The Immune System

     
     https://link.springer.com/article/10.1007%2Fs00204-016-1797-5

    https://link.springer.com/article/10.1007%2Fs00204-016-1797-5

     

    Bio-corona can act as danger signals to the immune system and cause an inflammatory reaction by the immune system (via activation of TLRs on antigen presenting cells) possibly by nanoparticle-associated molecular patterns (NAMPs). R R R

    Bio-corona can also the innate immune system via complement activation (via lectin pathway) and key effector cells (such as mast cells). R R

    Biocorona and NPs can also act as haptens and activate the immune system. R

    3. May Contribute To Autoimmunity Or Cancer

     
     https://link.springer.com/article/10.1007%2Fs00204-016-1797-5

    https://link.springer.com/article/10.1007%2Fs00204-016-1797-5

     

    Biocorona may also sway the immune system. R

    For example, if bio-corona solely activates helper T lymphocytes type 1 (Th1), B lymphocytes and macrophages type 1 (M1), then the immune system may be stuck in an acute inflammatory reaction. R

    On the other hand, if bio-corona solely activates helper T lymphocytes type 2 (Th2), M2 and regulatory T lymphocytes (Tregs), then the immune system can sustain a chronic inflammatory response, thus producing possible pro-tumor activity. R

    4. Can Worsen Endotoxin Exposure

    Some biocorona can bind to lipoplysaccharides (LPS) and enhance LPS's pro-inflammatory actions. R R R

    5. Can Go By Undetected By The Immune System

    Bio-corona may also have ways to go by undetected by the immune system. R

    For example, spores of the human opportunistic fungal pathogen Aspergillus fumigatus are surrounded by a natural protein corona of hydrophobin, making them “invisible” to cells of the immune system. R

    This provides further evidence that bio-corona can be have stealth-like properties. R

    6. Other Systems Affected

     
     https://www.sciencedirect.com/science/article/pii/S0041008X15301368

    https://www.sciencedirect.com/science/article/pii/S0041008X15301368

     
    • Brain - Biocorona can help transport NP across the Blood-Brain Barrier (BBB). R R
    • Gut - can alter the gut-brain axis and other microbiome-(human)host interactions R
    • Kidneys - possible cell death from gold biocorona formation R R
    • Liver R R
    • Lungs R
    • Spleen R
    • Vascular system - possible DNA damage and repair, heat shock response, mitochondrial energy metabolism, oxidative stress and antioxidant response, and ER stress and unfolded protein response cascades; e.g. iron biocorona increases  IL-6, TNF-α, Cxcl-2, VCAM-1, and ICAM-1 R R

    What To Do About Bio-Corona?

     
     

    What may help with toxic bio-corona complexes?

    • Albumin - can inhibit NPs R
    • ApoE - Apolipoprotein E can bind to NPs, although it can also help NPs cross the BBB R R R
    • ApoA1 R
    • Avoid exposure to nanomaterials, nanoparticles, and ultrafine particulate matter.
    • N-Acetyl Cysteine (NAC) - can reduce oxidative stress by blocking macrophage activation R

    Mechanism Of Action

    Hard vs Soft Biocorona:

    • "Due to the large surface area, nanosize biomaterials have high free energy which has the tendency to dynamically interact with molecular entities present in the surrounding. Proteins are the major entity strongly interacts with the surface of nanoparticles. As soon as a nanomaterials is in contact with biological fluid, proteins are adsorbing on the surface forming a surrounding layer. The binding of this layer is assumed to be tight, however reversible, resulting in a dynamic exchange of proteins with the microenvironment. The protein layer, is also called biocorona, and is composed of a hard corona and a soft corona, characterized by a slow exchange and a fast exchange, respectively, of proteins. Interestingly it has been observed that among the 3,400 proteins of human plasma only a minor part of them is directly interacting with nanoparticles" R

    Biocorona and Toll-Like Receptors: R

    • NPs can act as danger signals because pathogens display PAMPs and damaged tissues release DAMPs that act as a secreted alarmin.
    • NPs coated with bio-corona of complex protein structure can act as nanomaterial-associated molecular patterns (NAMPs).
    • These molecular signatures are recognized by pattern recognition receptors (PRRs), including innate immunity Toll-like receptors (TLRs).
    • The activation of PRRs triggers inflammation and alerts the adaptive immune system to an imminent danger.
    • Thus, NPs coated with bio-corona, displaying hydrophobic surfaces, are interpreted as danger signals by the immune system