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Chemically Modified Nucleic Acid Nanodevices: Molecular Engineering for Drug Delivery; Theranostics; Biosensing and Diagnostics
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PRE
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DOI：10.1039/D6CC01064D.png)
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Abstract
En 中文
The intrinsic programmability of nucleic acids has positioned them as versatile molecular building blocks for constructing nanodevices with significant diagnostic and therapeutic potential.However; the clinical translation of these constructs is severely hindered by major pharmacokinetic (PK) and biophysical limitations; including susceptibility to enzymatic degradation; short circulation half-life; and inefficient cellular uptake. Chemical modification; encompassing nucleobase engineering; backbone and sugar-ring alterations; terminal conjugation; and higher-order structural reinforcement; provides a powerful strategy to overcome these barriers by enhancing in vivo stability; prolonging circulation; improving cellular internalization; and enabling stimulus-responsive cargo release. In this review; we summarize recent advances in chemically modified nucleic acid nanodevices; focusing on how specific chemical designs modulate physicochemical properties; improve pharmacokinetics; enable organ-or cell-selective targeting; and enable spatiotemporally controlled molecular release. We further highlight their emerging applications in precision drug delivery; high-sensitivity biosensing; and integrated theranostics. Finally; we critically discuss persistent translational challenges; including batch-to-batch scalability; immunogenicity; and longterm nanotoxicity; and propose forward-looking solutions; such as AI-assisted design; to pave the way for industrial adoption and clinical implementation.
Keywords:
Nucleic acid nanodevices
Chemical modification
Drug delivery
Theranostics
Biosensing