ROS-responsive hydrogel nanoarmor enables stepwise photodynamic viral inactivation and sustained anti-inflammation...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Virology

Background:

• Current monkeypox virus (MPXV) treatments struggle with drug resistance and cannot address both viral replication and inflammatory responses.
• A dual therapeutic strategy is needed to simultaneously combat viral load and excessive inflammation during MPXV infection.

Purpose of the Study:

• To develop an innovative dual hydrogel system for MPXV treatment, combining phototherapy for virus clearance and immunomodulation for inflammation control.
• To evaluate the efficacy of this dual hydrogel system in MPXV-infected animal models.

Main Methods:

• Constructed a dual hydrogel system embedding aggregation-induced emission (AIE) nanoparticles in a ROS-degradable PVA-tsPBA hydrogel and loading Dexamethasone (DXMS) into a zwitterionic SBMA hydrogel.
• Utilized near-infrared laser irradiation to activate AIE nanoparticles, generating ROS for MPXV inactivation and hydrogel degradation.
• Assessed viral inhibition, inflammation reduction, and wound healing in mouse, rabbit, and non-human primate models of MPXV-induced skin damage.

Main Results:

• The dual hydrogel system effectively generated ROS, destroying the MPXV shell and inactivating the virus.
• Post-viral clearance, sustained release of DXMS from the SBMA hydrogel suppressed pro-inflammatory cytokines and reduced tissue damage.
• Significant inhibition of viral replication and accelerated wound healing were observed in MPXV-infected animal models.

Conclusions:

• The developed dual hydrogel nanoparticle system offers a transformative therapeutic platform for MPXV by precisely clearing the virus and mitigating inflammation.
• This convertible platform shows potential for treating MPXV and other highly inflammatory viral infections, addressing limitations of current treatments.