Multifunctional carbon dot-based photonic nanomedicinal platforms다기능성 탄소점 기반 광매개형 나노의약 플랫폼 연구

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Carbon dots (CDs), a relatively new class of carbon-based nanomaterials, are emerging as a photonic nanomedicine due to many advantages, such as unique optical properties, high photostability, good aqueous solubility, and superior biocompatibility compared to classical photosensitizers or heavy metal‐based quantum dots. This thesis describes the design and therapeutic strategies of CDs for the photo-mediated treatments of diseases, especially for amyloid-associated diseases including Alzheimer’s disease (AD). The implementation of CDs-based nanoplatforms against amyloidosis is addressed to present CDs’ potency as a promising photonic nanomedicine. Chapter 1 elucidates carbon dots (CDs) and their attractive photophysical and physicochemical properties such as tunable absorption/photoluminescence from ultraviolet to near-infrared, high photostability, biocompatibility, and aqueous dispersity. This chapter describes the fundamental photophysical properties of CDs and highlights their recent applications to bioimaging, photomedicines (e.g., photodynamic/photothermal therapies), biosensors (e.g., fluorometric biosensing, photoelectrochemical biosensing), and healthcare devices. Chapter 2 demonstrates the application of CDs as effective inhibition/disaggregation agents against $\beta$ ‐amyloid ($A\beta$) self-assembly. The CDs, which were synthesized using ammonium citrate and passivated with branched polyethylenimine (bPEI), exhibit cationic surface characteristics and visible light absorbability to suppress the aggregation of $A\beta$ peptides. Under light illumination, the CDs display a strong effect on $A\beta$ aggregation inhibition and on the dissociation of $\beta$‐sheet‐rich assemblies through the generation of reactive oxygen species. The results show that CDs’ photoactivation and a series of photo-mediated events significantly alleviate $A\beta$‐mediated neurotoxicity. Chapter 3 describes multifunctional CDs as a therapeutic nanoagent for modulating Cu(II)-mediated $A\beta$ aggregation. o-Phenylenediamine derived CDs possess nitrogen (N)-containing polyaromatic functionalities on their surface, inducing coordination with Cu(II) that has high relevance to AD pathogenesis. This chapter investigates the CDs’ multiple capabilities that can chelate Cu(II) ions, suppress $A\beta$ aggregation, and photooxygenate $A\beta$ peptides, for the inhibitory strategies against Cu(II)-mediated $A\beta$ aggregation. In Chapter 4, $A\beta$ targeting CDs and their use in photomodulation modality are demonstrated to inhibit toxic $A\beta$ aggregation in vivo. The transgenic mice that co-express five familial AD mutations (i.e., 5xFAD) are employed as in vivo models. The stereotaxically injected CDs bind with $A\beta_{42}$ peptides/aggregates in 5xFAD mice brains and induce photooxygenation of $A\beta$ peptides under 617 nm light irradiation, impeding the formation of $\beta$-sheet rich $A\beta$ aggregates. This chapter presents the in vivo photomodulation operations using CDs and their strong potential as an alternative photonic nanomedicinal platform for anti-amyloidosis.
Advisors
Park, Chan Beumresearcher박찬범researcher
Description
한국과학기술원 :신소재공학과,
Publisher
한국과학기술원
Issue Date
2020
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 신소재공학과, 2020.8,[ix, 131 p. :]

Keywords

carbon dots▼aphotonic nanomaterials▼ananomedicine▼aphotoexcitation; photoinduced effects▼abeta-amyloid; 탄소점▼a광학 나노 소재▼a나노의약▼a광여기▼a광매개 현상▼a베타-아밀로이드

URI
http://hdl.handle.net/10203/284486
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=926270&flag=dissertation
Appears in Collection
MS-Theses_Ph.D.(박사논문)
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