Treatment of Surgical Brain Injury by Immune Tolerance Induced by Peripheral Intravenous Injection of Biotargeting Nanoparticles Loaded With Brain Antigens

Abstract

Once excessive, neurological disorders associated with inflammatory conditions will inevitably cause secondary inflammatory damage to brain tissue. Immunosuppressive therapy can reduce the inflammatory state, but resulting infections can expose the patient to greater risk. Using specific immune tolerance organs or tissues from the body, brain antigen immune tolerance treatment can create a minimal immune response to the brain antigens that does not excessively affect the body's immunity. However, commonly used immune tolerance treatment approaches, such as those involving the nasal, gastrointestinal mucosa, thymus or liver portal vein injections, affect the clinical conversion of the therapy due to uncertain drug absorption, or inconvenient routes of administration. If hepatic portal intravenous injections of brain antigens could be replaced by normal peripheral venous infusion, the convenience of immune tolerance treatment could certainly be greatly increased. We attempted to encapsulate brain antigens with minimally immunogenic nanomaterials, to control the sizes of nanoparticles within the range of liver Kupffer cell phagocytosis and to coat the antigens with a coating material that had an affinity for liver cells. We injected these liver drug-loaded nanomaterials via peripheral intravenous injection. With the use of microparticles with liver characteristics, the brain antigens were transported into the liver out of the detection of immune armies in the blood. This approach has been demonstrated in rat models of surgical brain injury. It has been proven that the immune tolerance of brain antigens can be accomplished by peripheral intravenous infusion to achieve the effect of treating brain trauma after operations, which simplifies the clinical operation and could elicit substantial improvements in the future.

RETRACTED: Oral Administration of Brain Protein Combined With Probiotics Induces Immune Tolerance Through the Tryptophan Pathway

“…Through specific immune-tolerant organs or tissues from the body, brain antigen-induced immune tolerance can create a minimal immune response to brain antigens that does not excessively affect the body's immunity (Tian et al, 2019). Immune tolerance is established in multiple ways, such as the oral administration or injection of autologous brain antigens via the thymus and liver, and each method has advantages and disadvantages.…”

Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities

“…In addition to increasing the ratio of PBAE to other polymers, varying polymer properties such as lipophilicity has also been shown to enhance transfection [89]. PBAE/polyester particle blends have been used for delivery of other cargo, including small molecule drugs and biologics, exploiting favorable properties of PBAEs like pH-responsive triggered release and rapid degradation [90][91][92][93], and PBAE has also been explored as a porogen in PLGA-based scaffolds for the release of multiple agents on different timescales [94][95][96].…”

Functional recovery following traumatic brain injury in rats is enhanced by oral supplementation with bovine thymus extract

“…[30][31][32][33] In fact, induction of immune tolerance is one of the proposed novel approaches toward treating neurodegenerative diseases, TBI, and also surgical brain injury, where delivery of nervous system antigens through oral, nasal mucosa or intravenous routes was shown to reduce inflammation and offer neuroprotection. [33][34][35] Hence, the presence of serum IgG antibodies against food-derived antigens is considered a marker of immune tolerance associated with the production and activation of regulatory T cells (Treg) and not a marker of food sensitivity or intolerance. 36 Nutritional support is considered a plausible approach toward ameliorating, and possibly preventing, the long-term consequences of head injury.…”