pH-responsive delivery of H2 through ammonia borane-loaded mesoporous silica nanoparticles improves recovery after spinal cord injury by moderating oxidative stress and regulating microglial polarization

Abstract

Imbalance of oxidative and inflammatory regulation is the main contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury (SCI). As an emerging biosafe strategy for protecting against oxidative and inflammatory damage, hydrogen (H2) therapy is a promising approach for improving the microenvironment to allow neural regeneration. However, achieving release of H2 at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H2. Thus, we assembled SiO2@mSiO2 mesoporous silica nanoparticles and loaded them with ammonia borane (AB), which has abundant capacity and allows controllable release of H2 in an acid-dependent manner. The release of H2 from AB/SiO2@mSiO2 was satisfactory at pH 6.6, which is approximately equal to the microenvironmental acidity after SCI. After AB/SiO2@mSiO2 were intrathecally administered to rat models of SCI, continuous release of H2 from these nanoparticles synergistically enhanced neurofunctional recovery, reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction. Furthermore, in the subacute phase of SCI, microglia were markedly polarized toward the M2 phenotype by H2 via inhibition of TLR9 expression in astrocytes. In conclusion, H2 delivery through AB/SiO2@mSiO2 has the potential to efficiently treat SCI through comprehensive modulation of the oxidative and inflammatory imbalance in the microenvironment.

Mesoporous Silica-Based Nanoplatforms Are Theranostic Agents for the Treatment of Inflammatory Disorders

“…AB/mSiO 2 administration significantly controlled the excess ROS and regulated acute inflammation. These results cumulatively show that AB/mSiO 2 nanoparticles can be a potential therapeutic agent to treat neuronal inflammation after SCI [ 116 ].…”

“…Spinal cord injury (SCI) is a neural inflammation condition characterized by an imbalanced inflammatory and oxidative condition of neurons, leading to delayed rebuilding or failure to rebuild the damaged neural networks. So far, hydrogen (H 2 ) therapy can treat the spared neurons and allow the neuronal niche to develop new neuronal cells [ 116 ].…”

Recent advances in nanomaterials for the treatment of spinal cord injury

“…(C) Shield transportation of ammonia borane for responsive H 2 release. Copyright 2021 Regenerative Biomaterials [ 86 ]. (D) Macrophage-mediated degradable gelatin-coated MSN sturcture carrying pirfenidone for controlled release in SCI treatment.…”

“…Liu et al. [ 86 ] constructed ammonia borane-loaded MSNs. The drug-loaded MSNs were sensitive to acidic pH in SCI, and then ammonia borane decomposed to release H 2 gas, exerting a regulatory effect on oxidative and inflammatory imbalance ( Fig.…”

Hydrogen Promotes the Effectiveness of Bone Mesenchymal Stem Cell Transplantation in Rats with Spinal Cord Injury

“…H 2 has shown good therapeutic effects in the treatment of various diseases, such as diabetes, sepsis, atherosclerosis, hypertension, and cancer [ 23 – 25 ]. H 2 direct inhalation and hydrogen-rich water have been used in the treatment of SCI with good therapeutic effects [ 26 – 30 ]. H 2 can improve the microenvironment imbalance by suppressing inflammatory responses and oxidative stress levels in SCI areas.…”