Rationally designed upconversion nanoparticles for NIR light-controlled lysosomal escape and nucleus-based...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Photodynamic therapy (PDT) is a promising cancer treatment.
• Designing photosensitizers that target the cell nucleus remains a challenge.
• Developing effective nucleus-targeting strategies is crucial for enhancing PDT efficacy.

Purpose of the Study:

• To develop a novel nucleus-targeting strategy for photodynamic therapy.
• To utilize a "one treatment, multiple irradiations" approach for enhanced cancer treatment.
• To investigate the anticancer performance of engineered nanoparticles in various cell models.

Main Methods:

• Fabrication of rose bengal (RB)-loaded upconversion nanoparticles coated with mesoporous silica and amine groups (UCNP/RB@mSiO2-NH2 NPs).
• Utilizing the "one treatment, multiple irradiations" strategy involving sequential near-infrared light exposure.
• Investigating nanoparticle accumulation in lysosomes and subsequent nuclear transfer for nucleus-based PDT.

Main Results:

• Engineered UCNP/RB@mSiO2-NH2 NPs specifically accumulated in acidic lysosomes due to surface amine groups.
• Initial near-infrared irradiation triggered lysosomal destruction and nanoparticle release.
• Released nanoparticles successfully transferred to the nucleus, enabling nucleus-based PDT with significant anticancer effects.
• Demonstrated excellent anticancer performance in both 2D and 3D cell models.

Conclusions:

• The developed "one treatment, multiple irradiations" strategy effectively achieves nucleus-based photodynamic therapy.
• The rationally designed UCNP/RB@mSiO2-NH2 NPs show significant potential for advanced cancer treatment.
• This approach overcomes challenges in designing nucleus-targeting photosensitizers for enhanced therapeutic outcomes.