A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite
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Updated: Feb 10, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Zhengze Yu1, Yegang Ge1, Qiaoqiao Sun1
1College of Chemistry, Chemical Engineering and Materials Science , Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong , Key Laboratory of Molecular and Nano Probes , Ministry of Education , Institute of Molecular and Nano Science , Shandong Normal University , Jinan 250014 , P. R. China . Email: lina@sdnu.edu.cn ;
Abstract:
Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen (1O2) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.
Insights
This study introduces a novel DNA/upconversion nanocomposite for precise cancer targeting and photodynamic therapy (PDT). The strategy prevents off-target effects by masking folic acid (FA) until it reaches the acidic tumor environment, enhancing therapeutic efficacy.
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.
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