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대한화학회 창립 75주년
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05월 20일 18시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능
제125회 대한화학회 학술발표회 및 총회
Zwitterionic Surfaced Nanoparticles for Biomedical Applications
2020년 2월 18일 15시 10분 11초
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화 14시 : 30분
Life Chemistry -
Current issues in Nanobio Science
Sung Jee Kim
Department of Chemistry, Pohang University of Science and Technology, Korea
A few biomedical applications using zwitterionic surfaced nanoparticles will be introduced, which will encompass sensing, imaging, and cancer therapy. pH-responsive generation of unevenly zwitterioninc surfaced gold nanoparticles is introduced, which we named "smart" gold nanoparticle. It is designed to aggregate in mild acidic intracellular environments by its hydrolysis-susceptible citraconic amide surface. With a relatively small size of a few to 10 nm, the "smart" gold nanoparticles can be efficiently internalized into cancerous cells. Electrostatic attractions between the nanoparticles can rapidly form aggregates inside the cells, and the aggregates accumulate as the exocytosis is blocked by the increased size. The pH-induced formation of aggregates shifts the absorption to far-red and near-infrared. The absorption shift to longer wavelength is used for photothermal cancer therapy as it guarantees maximal tissue penetration for potential therapeutic applications. The photothermal response retained upon continued laser irradiation as contrary to the case of gold nanorods. A challenge in using plasmonic nanostructure–drug conjugates for thermo–chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Doxorubicin conjugated smart gold nanoparticles were used for spatiotemporally concerted cancer therapy at the cellular and organ levels. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. Using an animal model, effective tumor growth suppression is demonstrated. The smart gold nanoparticles were also used for imaging probes: simultaneous Raman imaging, photothermal optical coherence tomography, and photoacoustic imaging. Wrapping smart gold nanoparticles using liposome or mesenchymal stem cells are also introduced, which enhanced systemic circulation and tumor accumulation. On the other hand, evenly distributed zwitterionic surface greatly reduced non-specific adsorptions on nanoparticles. Quantum dots were conjugated to tumor-specific antibodies with zwitterionic surface were used to diagnose tumors for sectioned mouse tissues, fresh mouse colons stained ex vivo and in vivo, and also for fresh human colon adenoma tissues. The probes successfully detected not only cancers that are readily discernible by bare eyes but also hyperplasia and adenoma regions. Multiplexed QD, spray-and-wash, and endoscopy approach provided a significant advantage for detecting small or flat tumors that may be missed by conventional endoscopic examinations. QD-Ab probe was also used in conjunction with a ratiometric fluorescent molecular probe, cresyl violet–glutamic acid derivative, that ratiometrically switches between two fluorescent colors in response to the enzyme activity of λ-glutamyltranspeptidase. Co-application of the two kinds of probes, QD-Abs and the ratiometric molecular probe, afforded accurate visualization of carcinomas, hyperplasia and adenoma regions.
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