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Programmable DNA Nanospheres for Photothermal-Controlled Intracellular Protein Degradation.

Yu Chen1,2, Zongkang Guo2, Hang Xiao2

  • 1Department of Orthopedics, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, P.R. China.

Angewandte Chemie (International Ed. in English)
|November 10, 2025
PubMed
Summary
This summary is machine-generated.

This study introduces a novel DNA nanosphere for targeted protein degradation in cancer cells. The system uses photothermal therapy to eliminate cancer-promoting proteins, enhancing treatment efficacy.

Keywords:
DNA nanospheresIntracellular protein degradationPhotothermal controlSynergistic cancer therapy

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Cancer Therapy

Background:

  • Photothermal-controlled protein degradation is a novel strategy for intracellular protein elimination.
  • Current systems face challenges with low bioavailability and nonspecific distribution, limiting therapeutic effectiveness.

Purpose of the Study:

  • To develop a programmable, photothermal-responsive DNA nanosphere for targeted and spatiotemporally controlled intracellular protein degradation.
  • To overcome limitations of existing photothermal systems for enhanced cancer therapy.

Main Methods:

  • A modular DNA nanosphere was designed, integrating a tumor-targeting aptamer, a glutathione (GSH)-responsive linker, and a degradation unit.
  • The nanosphere selectively accumulates in tumor cells, disassembles in the cytoplasm, and releases degradation modules.
  • Laser irradiation triggers localized heating to disrupt protein conformation and activate autophagy-lysosomal clearance.

Main Results:

  • The strategy achieved efficient programmed death-ligand 1 (PD-L1) degradation in various cancer cell models.
  • The system demonstrated adaptability for degrading other targets like vascular endothelial growth factor (VEGF).
  • Synergistic antitumor effects were observed when combined with mild phototherapy.

Conclusions:

  • The developed DNA nanosphere platform offers improved tumor selectivity, cellular permeability, and in vivo stability.
  • This multifunctional and modular design presents a translatable solution for intracellular protein degradation-based cancer therapy.
  • The system shows promise for targeted cancer treatment by precisely controlling protein elimination.