i-Motif in Cancer Diagnosis and Treatment: Fabrication and Functionalization

Abstract

As a four-stranded DNA structure which forms within cytosine(C)-rich sequences, i-Motif, introduces a state-of-the-art pH-responsive targeting agent having remarkable ability in drug delivery systems (DDSs). Upon exposing to the slightly acidic environment, these sequences present significant tendency to fold into the intramolecular i-motif structure, normally with three loop style, supplying potent drug carriers. The conformational flexibility, easy modification, symmetrical architecture, and intrinsic biocompatibility of C-rich sequences, powerfully support their usage in drug delivery applications. Particularly, conjugation of C-rich with different inorganic nanoparticles or organic fragments improves their efficacy as nanocarriers by providing increased biocompatibility, reduced cytotoxicity, and enhanced stability. The i-motif-based systems are hired for both their cancer detection and therapeutic interventions. Despite the fact that utilizing the i-motifs has opened a shining topic in the usage of pH-responsivity, there is still a lack of thorough review which specifically analyzes the progresses of this materials in constituting targeted/non-targeted DDSs and biosensors. In this timely update we aim to supply an in-depth analysis of these progresses, with the goal of inspiring innovative strategies for designing targeting/non-targeting systems that benefitted from i-motifs as pH-responsive agents in combination with different types of nanocarriers for enhanced cancer diagnosis and treatment.

Article information

Article type
Review Article
Submitted
07 May 2025
Accepted
08 Oct 2025
First published
23 Oct 2025

J. Mater. Chem. B, 2025, Accepted Manuscript

i-Motif in Cancer Diagnosis and Treatment: Fabrication and Functionalization

J. Zamanian, A. Samie, H. Alavian, M. Alibolandi, L. Etemad, K. Abnous and S. M. Taghdisi, J. Mater. Chem. B, 2025, Accepted Manuscript , DOI: 10.1039/D5TB01085C

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