TY - JOUR
T1 - Near-infrared plasmonic assemblies of gold nanoparticles with multimodal function for targeted cancer theragnosis
AU - Kim, Seong Eun
AU - Lee, Bo Ram
AU - Lee, Hohyeon
AU - Jo, Sung Duk
AU - Kim, Hyuncheol
AU - Won, You Yeon
AU - Lee, Jeewon
N1 - Funding Information:
This study was supported by the 2015 NLRL (National Leading Research Lab.) Project (grant no. NRF-2015R1A2A1A05001861) of the National Research Foundation of Korea (NRF), the Bio & Medical Technology Development Program of the NRF funded by the Ministry of Science & ICT (grant no. NRF-2017M3A9F5032628) and the Basic Science Research Program through the NRF grant funded by the Korean Government (MEST) (grant no. NRF-2017R1A5A1070259). The contributions of SDJ and YYW were supported by the Global Innovative Research Center (GiRC) Program (2012k1A1A2A01056095) of the Korea Institute of Science and Technology (KIST). We would also like to thank Dr. Kwangmyeong Kim at KIST for kindly donating A431 cells.
PY - 2017
Y1 - 2017
N2 - 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_5mCG, DMA_9mCG, and DMA_21mCG), among which DMA_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_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.
AB - 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_5mCG, DMA_9mCG, and DMA_21mCG), among which DMA_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_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.
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U2 - 10.1038/s41598-017-17714-2
DO - 10.1038/s41598-017-17714-2
M3 - Article
C2 - 29229979
AN - SCOPUS:85054095227
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 17327
ER -