Self-Generative Singlet Oxygen (1O2)-Initiated Chemical Modification of Nuclear DNAs Combats Tumor Drug Resistance

May 22, 2026

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Multidrug resistance (MDR) undermines chemotherapy by limiting drug action and promoting efficient detoxification and damage repair. A self-generative singlet oxygen (1O2)-initiated chemical modification of nuclear DNAs (SiCMoND) strategy synergizes with chemotherapy to disable MDR tumor cells. Tumor-targeted nano-bombs (FA(CT-fT-Dox)) release Cu-TCPP and fTAT-Dox under tumor microenvironment disassembly; Cu-TCPP converts H2O2 to 1O2 and triggers covalent cyclization with DNA nucleobases, causing severe DNA damage and restoring therapeutic susceptibility. Sustained intranuclear Dox release suppresses transcription/translation and drives apoptosis. In vivo, FA(CT-fT-Dox) outperforms a DNA-modification–free counterpart with 83.3% tumor suppression in MCF-7/ADR tumors.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

Abstract

Introduction

Multidrug resistance challenges in chemotherapy

Existing strategies to overcome MDR

Limitations of gene interference and targeted nanodrugs

Scheme and Figures overview

SiCMoND approach schematic

1O2 generation and nanoparticle characterization

Cellular retention and molecular mechanism readouts

FAQs

What is the core idea of the SiCMoND approach described in the document?

The approach uses self-generative singlet oxygen (1O2) to initiate covalent chemical modification of nuclear DNAs, thereby amplifying DNA damage and increasing tumor susceptibility to chemotherapy.

How are Cu-TCPP and fTAT-Dox delivered to the tumor and released?

Tumor-targeted FA(CT-fT-Dox) nanoparticles accumulate at the tumor site and undergo disassembly in the tumor microenvironment, releasing Cu-TCPP and fTAT-Dox simultaneously.

What outcome is reported for the multidrug-resistant MCF-7/ADR tumor model?

In vivo results show FA(CT-fT-Dox) achieves stronger antitumor efficacy than the DNA-modification–free control, with 83.3% tumor suppression and a 1.6-fold improvement in efficacy.

May 22, 2026

Upload by Logic