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G-quadruplexes as therapeutic platforms for anticancer drug delivery: from intrinsic cytotoxicity to drug delivery and nanotechnology
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DOI：10.1080/17425247.2026.2659926.png)
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Abstract
En 中文
G-quadruplexes have emerged as a versatile class of oligonucleotides that combine molecular recognition, intrinsic anticancer activity and drug carrier functions, offering new opportunities to improve tumor selectivity and overcome limitations of conventional chemotherapy.
This review summarizes structural and biological features that make G-quadruplexes attractive platforms for anticancer drug delivery, including cancer-selective uptake, high stability and scaffold versatility. We discuss G-quadruplexes with intrinsic antiproliferative activity, covalent G-quadruplex-drug conjugates including small molecules and nucleoside antimetabolites and G-quadruplexes that non-covalently host G-quadruplex ligands. We further examine G-quadruplex-decorated nanoparticles and DNA nanostructures, as well as, higher-order G-quadruplex architectures that enable multivalent receptor targeting. A literature search was conducted using the Web of Science database to identify peer-reviewed publications related to ‘G-quadruplex.’ The search covered the period from 2000 to the present (as of 12 January 2026).
G-quadruplexes represent a platform with unique capacity to unify targeting and therapy, offering a promising alternative to antibody-based systems. However, issues such as structural polymorphism, pharmacokinetics, and controlled drug release must be addressed through rational design and chemical modification to fully translate these delivery systems into clinically relevant anticancer therapeutics.
Keywords:
Aptamer-drug conjugates
anticancer drug delivery
G-quadruplex
nanoparticles
nucleic acid therapeutics
oligonucleotide targeting
tumor targeting
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