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.
탄소점은 0차원의 탄소 기반 나노 소재로, 친환경 탄소 전구체로 합성이 가능하고 그 과정 또한 용이하여 다양한 전구체에 따른 물리 화학적 특성과 생체 적합성 소재로써의 응용 가능성이 활발히 연구되었다. 특히 탄소점은 반도체적 특성과 조절 가능한 발광성을 가지는 광학 나노 소재이기도 하여, 기존 바이오 이미징이나 광매개 치료를 수행하던 광감응제 혹은 무기 양자점을 대체할 새로운 광의약제로 각광받고 있다. 본 학위 논문에서는 탄소점의 광학적 특성과 다양한 물성을 바탕으로 광매개 나노의약 플랫폼 개발을 위한 연구를 다루었다. 구체적으로, 알츠하이머병과 같은 퇴행성 뇌 질환을 표적으로 하여, 발병의 원인이 되는 독성의 베타-아밀로이드 자가조립을 효과적으로 억제하기 위한 다양한 탄소점 기반의 나노의약을 설계하고 그 응용 결과를 분석하였다. 0차원의 작은 탄소점은 베타-아밀로이드 펩타이드와 상호작용을 이루었고, 광여기 및 광매개 현상을 통해 베타-아밀로이드 펩타이드를 비가역적으로 변성 시켜 추후 응집을 막고 세포 독성을 크게 저감하였다. 최종 단계로 광매개성 베타-아밀로이드 펩타이드 응집 저해 기능에 베타-아밀로이드 표적성까지 부여한 카본닷 기반 나노의약을 알츠하이머성 동물 모델에 투여하였고, 광 조사를 통해 생체 뇌 속 베타-아밀로이드 펩타이드 응집에 대한 효과적 억제를 구현하여 질병 치료를 위한 차세대 광매개형 나노의약 플랫폼을 제시하였다.
