Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells

Mirza Muhammad Faran Ashraf Baig, Jinwei Ma, Xiuli Gao, Muhammad Ajmal Khan, Atif Ali, Awais Farid, Abdul Wasy Zia, Sobia Noreen, Hongkai Wu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

This study aimed to develop a robust approach for the early diagnosis and treatment of tumors. Short circular DNA nanotechnology synthesized a stiff and compact DNA nanotubes (DNA-NTs) framework. TW-37, a small molecular drug, was loaded into DNA-NTs for BH3-mimetic therapy to elevate the intracellular cytochrome-c levels in 2D/3D hypopharyngeal tumor (FaDu) cell clusters. After anti-EGFR functionalization, the DNA-NTs were tethered with a cytochrome-c binding aptamer, which can be applied to evaluate the elevated intracellular cytochrome-c levels via in situ hybridization (FISH) analysis and fluorescence resonance energy transfer (FRET). The results showed that DNA-NTs were enriched within the tumor cells via anti-EGFR targeting with a pH-responsive controlled release of TW-37. In this way, it initiated the triple inhibition of "BH3, Bcl-2, Bcl-xL, and Mcl-1". The triple inhibition of these proteins caused Bax/Bak oligomerization, leading to the perforation of the mitochondrial membrane. This led to the elevation of intracellular cytochrome-c levels, which reacted with the cytochrome-c binding aptamer to produce FRET signals. In this way, we successfully targeted 2D/3D clusters of FaDu tumor cells and achieved the tumor-specific and pH-triggered release of TW-37, causing tumor cell apoptosis. This pilot study suggests that anti-EGFR functionalized, TW-37 loaded, and cytochrome-c binding aptamer tethered DNA-NTs might be the hallmark for early tumor diagnosis and therapy.

Original languageEnglish
Article number123988
JournalInternational Journal of Biological Macromolecules
Volume236
Early online date11 Mar 2023
DOIs
Publication statusPublished - 1 May 2023

Keywords

  • 2D/3D clusters of hypopharyngeal tumor cells
  • Cytochrome-c
  • DNA nanotubes
  • Early diagnosis of tumor
  • Small molecular drugs

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells'. Together they form a unique fingerprint.

Cite this