Near-Infrared Laser-Switching DNA Phase Separation Nanoinducer for Glioma Therapy.

in ACS nano by Yixin Chen, Huijing Xiang, Xiaodan Li, Yu Chen, Jun Zhang

TLDR

  • The study creates a special kind of nanoparticle that can help treat a type of brain tumor called gliomas. The nanoparticle can make a special kind of light that can damage the DNA in the tumor cells and stop them from growing. The study shows that the nanoparticle is very effective at stopping the tumor cells from growing. This could be a new way to treat gliomas.

Abstract

DNA phase separation participates in chromatin packing for the modulation of gene transcription, but the induction of DNA phase separation in living cells for disease treatment faces huge challenges. Herein, we construct a Ru(II)-polypyridyl-loaded upconversion nanoplatform (denoted as UCSNs-R) to achieve the manipulation of DNA phase separation and production of abundant singlet oxygen (O) for efficient treatment of gliomas. The utilization of the UCSN not only facilitates high loading of Ru(II)-polypyridyl complexes (RuC) but also promotes the conversion of near-infrared (NIR) laser to ultraviolet light for efficientOgeneration. The released RuC exhibit DNA "light-switch" behavior and high DNA binding affinity that induce phase separation of DNA in living cells, thus resulting in DNA damage and suppressing tumor-cell growth. In vivo investigation demonstrates the high capability of UCSNs-R in inhibiting tumor proliferation under NIR laser illumination. This work represents a paradigm for designing a DNA phase separation nanoinducer through integration of the UCSN with Ru(II)-polypyridyl-based complexes for efficient therapy of gliomas.

Overview

  • The study aims to investigate the manipulation of DNA phase separation and production of singlet oxygen (O) for efficient treatment of gliomas using a Ru(II)-polypyridyl-loaded upconversion nanoplatform (UCSNs-R).
  • The methodology used for the experiment involves the construction of UCSNs-R, which facilitates high loading of Ru(II)-polypyridyl complexes (RuC) and promotes the conversion of near-infrared (NIR) laser to ultraviolet light for efficientOgeneration. The released RuC exhibit DNA
  • The primary objective of the study is to demonstrate the high capability of UCSNs-R in inhibiting tumor proliferation under NIR laser illumination.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions, specifically the manipulation of DNA phase separation and production of singlet oxygen (O) using UCSNs-R. The results show that UCSNs-R induce phase separation of DNA in living cells, resulting in DNA damage and suppressing tumor-cell growth. The study demonstrates the efficiency of UCSNs-R in inhibiting tumor proliferation under NIR laser illumination, which is a significant finding compared to other methods of treating gliomas.

Implications and Future Directions

  • The study's findings suggest that UCSNs-R could be a promising tool for the treatment of gliomas. However, the study has limitations, such as the need for further in vivo studies to validate the results. Future research directions could include the development of UCSNs-R for other types of cancer and the optimization of the UCSN design for improved efficiency and specificity. Additionally, the study highlights the potential of using upconversion nanoparticles for the modulation of gene transcription and the production of singlet oxygen (O) for therapeutic purposes.
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