Secondary Structure-Dependent Physicochemical Interaction of Oligonucleotides with Gold Nanorod and Photothermal Effect for Future Applications: A New Insight

寡核苷酸与金纳米棒的二级结构依赖性物理化学相互作用和光热效应及其未来应用:新见解

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作者:Upasana Das, Aditi Sahoo, Subhash Haldar, Sudin Bhattacharya, Syam Sundar Mandal, William H Gmeiner, Supratim Ghosh

Abstract

We investigate the physicochemical interactions of gold nanorod (GNR) with single-stranded, double-stranded, and hairpin DNA structures to improve the biological compatibility as well as the therapeutic potential, including the photothermal effect of the conjugates. Studies have demonstrated that different DNA secondary structures, containing thiol group, have different patterns of physicochemical interaction. Conjugation efficiency of paired oligonucleotides are significantly higher than that of oligonucleotides with naked bases. Furthermore, hairpin-shaped DNA structures are most efficient in terms of conjugation and increased dispersion, with least interference on GNR near-infrared absorbance and photothermal effect. Our conjugation method can successfully exchange the overall coating of the GNR, attaching the maximum number of DNA molecules, thus far reported. Chemical mapping depicted uniform attachment of thiolated DNA molecules without any topological preference on the GNR surface. Hairpin DNA-coated GNR are suitable for intracellular uptake and remain dispersed in the cellular environment. Finally, we conjugated GNR with 5-fluoro-2'-deoxyuridine-containing DNA hairpin and the conjugate demonstrated significant cytotoxic activity against human cervical cancer cell line (KB). Thus, hairpin DNA structures could be utilized for optimal dispersion and photothermal effect of GNR, along with the delivery of cytotoxic nucleotides, developing the concept of multimodality approach.

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