In Situ Transformable Nanoplatforms with Supramolecular Cross-Linking Triggered Complementary Function for Enhanced...

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Nanoparticle cross-linking enhances therapeutic agent accumulation at tumor sites.
• Current nanoplatforms often feature independent components with limited biofunction amplification.

Purpose of the Study:

• To develop a tumor microenvironment-triggered, supramolecular coordination-induced nanoparticle cross-linking strategy for enhanced photodynamic therapy.
• To amplify the biofunctions of individual components within a nanoplatform.

Main Methods:

• Constructed transformable UCNP@MnOₓ-Hyp nanoparticles using lanthanide-doped upconversion nanoparticles (UCNPs), manganese oxide (MnOₓ), and hypericin (Hyp).
• Investigated nanoparticle transformation via reduction by glutathione and H₂O₂ in CT26 mouse colon cancer cells and xenograft tumors, leading to Mn²⁺ and Hyp release for in situ cross-linking.
• Evaluated the effect of Mn²⁺-Hyp coordination on Hyp absorbance, UCNP-Hyp energy transfer efficiency, and UCNP luminescence recovery.

Main Results:

• The Mn²⁺-Hyp coordination redshifted Hyp absorbance and improved UCNP-Hyp energy transfer efficiency by 5.6-fold.
• Supramolecular coordination-induced cross-linking enhanced UCNP luminescence recovery and increased intracellular accumulation of both UCNPs and Hyp.
• Photodynamic therapy efficacy was enhanced 2.1-fold at the cellular level and in vivo compared to non-cross-linked counterparts.

Conclusions:

• The developed strategy amplifies the biofunctions of nanoplatform components through responsive transformation.
• Supramolecular coordination-induced nanoparticle cross-linking offers a promising new approach for enhanced cancer therapy, particularly photodynamic therapy.