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.