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Tiny pH-Resolved DNA Nanospheres for Cellular Pyroptosis or Apoptosis Regulation
Yu Chen1, Xiaoyi Liu1, Yu Guo1
1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China.
Nano Letters
|October 1, 2024
Summary
Intelligent DNA nanospheres target cancer cells and distinguish pH changes to trigger cell death. Early endosome activation enhances antitumor efficacy via pyroptosis, offering a promising cancer therapy approach.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Developing nanomedicines for cancer therapy faces challenges in regulating programmed cell death.
- Precisely controlling cell death pathways like pyroptosis and apoptosis is crucial for enhanced antitumor efficacy.
Purpose of the Study:
- To design and synthesize intelligent DNA nanospheres (NS) that can differentiate endosomal pH.
- To regulate pyroptosis or apoptosis for improved cancer treatment outcomes.
Main Methods:
- Self-assembly of multifunctional DNA modules into nanospheres.
- Utilizing acid-responsive DNA sequences for targeted activation within endosomes.
- Employing photodynamic therapy (PDT) with singlet oxygen (¹O₂) generation upon laser irradiation.
Main Results:
- DNA nanospheres successfully distinguished pH differences between early endosomes (EE) and lysosomes (Ly).
- EE-activated PDT induced gasdermin-E-mediated pyroptosis, demonstrating superior antitumor efficacy.
- Lysosome-activated PDT induced apoptosis, showing less efficacy compared to pyroptosis.
Conclusions:
- Intelligent DNA nanospheres offer a novel platform for targeted cancer therapy.
- Endosome-specific activation of nanomedicines can precisely control cell death pathways.
- EE-activated pyroptosis presents a more effective strategy than Ly-activated apoptosis for cancer treatment.
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