Kinetically Gated and Self-Limiting Crystallization Enables Allosteric Phototheranostic Nanocrystals

Area of Science:

• Organic Chemistry
• Materials Science
• Nanotechnology
• Precision Medicine

Background:

• Crystalline organic nanomaterials offer potential for precision medicine due to their programmable photophysical functions.
• Controlled crystallization and responsive activation of these nanomaterials remain significant challenges.

Purpose of the Study:

• To develop a kinetically gated and self-limiting crystallization (KGSLC) strategy for constructing allosteric phototheranostic nanocrystals.
• To design organic nanocrystals with tumor microenvironment-triggered activation for enhanced phototherapy.

Main Methods:

• Rational molecular design incorporating TCF acceptor units and hydroxyl groups for controlled crystallization.
• Utilizing surface hydration and hydrogen-bond-assisted π-π stacking for highly crystalline assemblies.
• Synthesizing a disulfide-bridged prodrug ((HICyT)2S) for glutathione-triggered activation.

Main Results:

• The developed HICyT nanocrystals (HICyT NCs) exhibit strong near-infrared absorption and dual-type reactive oxygen species generation.
• The prodrug successfully converted into active HICyT NCs in the tumor microenvironment.
• The nanocrystals demonstrated deep-tissue penetration, albumin-activated NIR-I/II fluorescence, and potent in vivo tumor ablation.

Conclusions:

• The KGSLC strategy enables precise control over organic nanocrystal formation and function.
• The integrated platform offers spatiotemporal activation, real-time imaging, and effective phototherapy.
• This approach provides a promising route toward self-reporting phototheranostic materials for precision medicine.