Supramolecular Self-Assemblies with Spatiotemporal Controllable NO Release and Bioimaging Behavior toward...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapeutics

Background:

• Reactive nitrogen species (RNS)-based cancer therapy shows promise but faces challenges with nitric oxide (NO) and superoxide anion (•O2-) delivery due to short lifetimes and uncontrolled release.
• Effective codelivery and spatiotemporal control of these reactive species are crucial for enhancing therapeutic efficacy.

Purpose of the Study:

• To develop a light-activated supramolecular theranostic system for precise NO release and chemodynamic therapy (CDT) in cancer treatment.
• To integrate fluorescence imaging for real-time monitoring of the therapeutic process.
• To amplify the damage to tumor cells through a cascade reaction involving NO and reactive oxygen species (ROS).

Main Methods:

• Self-assembly of β-cyclodextrin-grafted hyaluronic acid (HA-CD) with a photoresponsive NO donor (Fc-NAp-NO) into nanocarriers.
• Loading nanocarriers with ascorbyl palmitate (PA) to provide hydrogen peroxide (H2O2) for CDT.
• Utilizing light irradiation to trigger NO release, initiate CDT, and enable fluorescence imaging.

Main Results:

• Achieved spatiotemporal control over NO release upon light irradiation.
• Successful integration of fluorescence imaging for theranostic applications.
• Generation of hydroxyl radicals (•OH) and superoxide anions (•O2-) via CDT, with •O2- reacting with NO to form cytotoxic peroxynitrite (ONOO-).
• Amplified RNS/ROS-induced damage to tumor cells, leading to enhanced therapeutic effects.

Conclusions:

• The developed light-activated nanocarrier system enables precise, imaging-guided, and cascade-enhanced tumor therapy.
• This platform overcomes the limitations of traditional RNS-based therapies by controlling the release and reaction of NO and ROS.
• The synergistic effect of NO, ROS, and ONOO- significantly enhances cancer treatment efficacy.