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Life sciences · Journal article
Acs Applied Nano Materials · October 29, 2026
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Abstract Vectors capable of oligonucleotide delivery and bioimaging, especially cell fate visualization, are highly desirable for effective cancer gene therapy. Herein, a dual-functional nucleic acid-targeted aggregation-induced emission (AIE) probe, namely, TPBI, was developed for small interfering RNA (siRNA) or antisense oligonucleotides (ASO) delivery and fluorescence imaging of cellular response. TPBI can self-assemble with oligonucleotides into nanocomplexes, exhibiting a ∼200-fold greater binding affinity for oligonucleotides than for BSA. High-affinity binding could prevent serum-induced dissociation of the nanocomplexes, facilitating stable oligonucleotide delivery and efficient gene silencing, whereas the polyethylenimine (PEI) vector lost efficacy in the serum. Beyond its vector role, the probe exhibited remarkable fluorescence enhancement upon binding to nuclear DNA, which enabled the specific labeling of dead cells. Notably, the distinct fluorescence patterns allowed for precise discrimination of cell cycle phases in fixed cells, offering a robust tool for cell proliferation analysis. In vivo studies using mice bearing the Hepa1−6−Luc hepatocellular carcinoma tumor demonstrated that the TPBI/siLUC nanocomplexes induced superior luciferase gene silencing relative to the PEI/siLUC complexes. The dual-functional AIE probe achieved efficient oligonucleotide delivery and in situ tracking of biological responses. Its assembled nanocomplexes exerted effective gene knockdown, showing considerable potential for high-efficiency tumor gene therapy.