Imaging of Cancer Cells and Dictated Cytotoxicity Using Aptamer-Guided Hybridization Chain Reaction (HCR)-Generated G-Quadruplex Chains

Amily Fang-Ju Jou; Yi-Te Chou; Itamar Willner; Ja-An Annie Ho

doi:10.1002/anie.202106147

Imaging of Cancer Cells and Dictated Cytotoxicity Using Aptamer-Guided Hybridization Chain Reaction (HCR)-Generated G-Quadruplex Chains

Angew Chem Int Ed Engl. 2021 Sep 27;60(40):21673-21678. doi: 10.1002/anie.202106147. Epub 2021 Aug 26.

Authors

Amily Fang-Ju Jou^{1

2}, Yi-Te Chou¹, Itamar Willner³, Ja-An Annie Ho^{1

4

5

6}

Affiliations

¹ Bioanalytical Chemistry and Nanobiomedicine Laboratory Department of Biochemical Science and Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.
² Department of Chemistry, Chung Yuan Christian University, No. 200, Chung Pei Road, Taoyuan City, 320314, Taiwan.
³ Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
⁴ Department of Chemistry, National (Taiwan) University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.
⁵ Center for Emerging Materials and Advance Devices, National (Taiwan) University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.
⁶ Center for Biotechnology, National (Taiwan) University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.

PMID: 34350685
DOI: 10.1002/anie.202106147

Abstract

DNA nanotechnology provides powerful tools for developing cancer theranostics. Here we introduce the autonomous surface-nucleolin-guided HCR that leads to the polymerization of G-quadruplex polymer chains, in which the Zn^II -protoporphyrin IX is intercalated. We demonstrate that MDA-MB-231 (Triple Negative Breast Cancer cells, TNBC) with overexpressed surface nucleolin were able to induce HCR leading to the formation of the Zn^II PPIX-loaded G-quadruplex polymer chains, while the M10 epithelial breast cells served as control. The Zn^II PPIX-loaded nanowires allow the selective imaging of TNBC, and their permeation into the TNBC leads to selective cytotoxicity and guided photodynamic therapy toward the cancer cells due to structural perturbation of the membranes. The aptamer-guided HCR-generated G-quadruplex polymer chains may serve as a versatile tool to target TNBC featuring poor prognosis and high pathological risk of recurrence, thus offering a promising theranostic platform.

Keywords: DNA nanotechnology; G-Quadruplex; hybridization chain reaction (HCR); photodynamic therapy; theranostic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Aptamers, Nucleotide / chemistry
Aptamers, Nucleotide / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Coordination Complexes / chemical synthesis
Coordination Complexes / chemistry
Coordination Complexes / pharmacology*
Drug Screening Assays, Antitumor
G-Quadruplexes
Humans
Nucleic Acid Hybridization
Protoporphyrins / chemistry
Protoporphyrins / pharmacology*
Triple Negative Breast Neoplasms / drug therapy*
Triple Negative Breast Neoplasms / pathology
Zinc / chemistry
Zinc / pharmacology*

Substances

Antineoplastic Agents
Aptamers, Nucleotide
Coordination Complexes
Protoporphyrins
protoporphyrin IX
Zinc