A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Folic acid (FA) targeted cancer therapy faces challenges due to folate receptor (FR) expression in normal tissues, leading to off-target effects.
• Existing strategies often result in unsatisfactory therapeutic outcomes and potential side effects.

Purpose of the Study:

• To develop a pre-protective strategy for precise tumor targeting and enhanced photodynamic therapy (PDT).
• To create a switchable DNA/upconversion nanocomposite triggered by the acidic tumor microenvironment.

Main Methods:

• Fabrication of a DNA/upconversion nanocomposite with polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs).
• Surface modification with FA and chlorin e6 (Ce6) functionalized DNA sequences of varying lengths.
• Utilizing a C-quadruplex formation in acidic conditions to expose FA for targeted binding and proximity-enhanced FRET for PDT.

Main Results:

• The nanocomposite demonstrated effective masking of FA in normal tissues and precise targeting in acidic tumor environments.
• Successful tumor-specific targeting was achieved through the interaction of exposed FA with FRs on cancer cells.
• Efficient generation of singlet oxygen (¹O₂) via FRET upon near-infrared light excitation.
• Significant inhibition of tumor growth observed in vivo due to enhanced targeting and PDT.

Conclusions:

• The switchable DNA/upconversion nanocomposite offers a promising pre-protective strategy for precise tumor targeting.
• This approach significantly improves the efficacy of photodynamic therapy by minimizing off-target accumulation.
• The developed system holds potential for advanced cancer treatment with reduced side effects.