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Here we report a novel assembly structure of near-infrared plasmonic gold nanoparticles (AuNPs), possessing both photoacoustic (PA) and photothermal (PT) properties. The template for the plasmonic AuNP assembly is a bioconjugate between short double-strand DNA (sh-dsDNA) and human methyl binding domain protein 1 (MBD1). MBD1 binds to methylated cytosine-guanine dinucleotides (mCGs) within the sequence of sh-dsDNA. Hexahistidine peptides on the engineered MBD1 function as a nucleation site for AuNP synthesis, allowing the construction of hybrid conjugates, sh-dsDNA-MBD1-AuNPs (named DMAs). By varying the length of sh-dsDNA backbone and the spacer between two adjacent mCGs, we synthesized three different DMAs (DMA&#95;5mCG, DMA&#95;9mCG, and DMA&#95;21mCG), among which DMA&#95;21mCG exhibited a comparable photothermal and surprisingly a higher photoacoustic signals, compared to a plasmonic gold nanorod. Further, epidermal growth factor receptor I (EGFR)-binding peptides are genetically attached to the MBD1 of DMA&#95;21mCG, enabling its efficient endocytosis into EGFR-overexpressing cancer cells. Notably, the denaturation of MBD1 disassembled the DMA and accordingly released the individual small AuNPs (<5 nm) that can be easily cleared from the body through renal excretion without causing accumulation/toxicity problems. This DMA-based novel approach offers a promising platform for targeted cancer theragnosis based on simultaneous PA imaging and PT therapy.

Purpose: Cationic lipid-coated gold nanoparticles were developed for efficient intracellular delivery of therapeutic siRNA., Methods: Particle formation was characterized by UV-visible spectroscopy, atomic force microscopy, and dynamic light scattering analysis. Cellular uptake, gene silencing effect, and cytotoxicity were investigated in multiple human cancer cell lines., Results: Nanoparticles had a spherical nanostructure with highly cationic surface charge and could form stable nanosized polyelectrolyte complexes with siRNA via electrostatic interactions; complexes exhibited efficient intracellular uptake and significant gene silencing effect with markedly low cytotoxicity compared to the widely used polycationic carrier, linear polyethyleneimine., Conclusions: We demonstrated that cationic lipid-coated gold nanoparticles could be widely utilized as efficient and safe siRNA nanocarriers for diverse therapeutic and diagnostic applications.