Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy

Key, Jaehong,Park, Kyeongsoon MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.3

<P>Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies.</P>

Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

Key, Jaehong,Dhawan, Deepika,Cooper, Christy L,Knapp, Deborah W,Kim, Kwangmeyung,Kwon, Ick Chan,Choi, Kuiwon,Park, Kinam,Decuzzi, Paolo,Leary, James F Dove Medical Press 2016 International journal of nanomedicine Vol.11 No.-

<P>While current imaging modalities, such as magnetic resonance imaging (MRI), computed tomography, and positron emission tomography, play an important role in detecting tumors in the body, no single-modality imaging possesses all the functions needed for a complete diagnostic imaging, such as spatial resolution, signal sensitivity, and tissue penetration depth. For this reason, multimodal imaging strategies have become promising tools for advanced biomedical research and cancer diagnostics and therapeutics. In designing multimodal nanoparticles, the physicochemical properties of the nanoparticles should be engineered so that they successfully accumulate at the tumor site and minimize nonspecific uptake by other organs. Finely altering the nano-scale properties can dramatically change the biodistribution and tumor accumulation of nanoparticles in the body. In this study, we engineered multimodal nanoparticles for both MRI, by using ferrimagnetic nanocubes (NCs), and near infrared fluorescence imaging, by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging.</P>

인공무릎관절 수술에서의 영역기반 ICP 알고리즘

기재홍(Jaehong Key),이문규(Moonkyu Lee),이창양(Changyang Lee),김동민(Dong M. Kim),유선국(Sun K. Yoo),최귀원(Kuiwon Choi) 한국정밀공학회 2006 한국정밀공학회 학술발표대회 논문집 Vol.2006 No.5월

Image Guided Surgery(IGS) system has been developed to provide exquisite and objective information to surgeons for surgical operation process. It is necessary that registration technique is important to match between 3D image model reconstructed from image modalities and the object operated by surgeon. Majority techniques of registration in IGS system have been used by recognizing fiducial markers placed on the object. However, this method has been criticized due to its invasive protocol inserting fiducial markers in patient"s bone. Therefore, shape-based registration technique using geometric characteristics of the object has been invested to improve the limitation of IGS system. During Total Knee Replacement(TKR) operation, it is challenge to register with high accuracy by using shape-based registration because the area to acquire sample data from knee is limited. We have developed region-based 3D registration technique based on anatomical landmarks on the object and this registration algorithm was evaluated in femur model. It was found that region-based algorithm can improve the accuracy in 3D registration. We expect that this technique can efficiently improve the IGS system.

Cu-Al Alloy Formation by Thermal Annealing of Cu/Al Multilayer Films Deposited by Cyclic Metal Organic Chemical Vapor Deposition

Hock Key Moon,Jaehong Yoon,김형준,이내응 대한금속·재료학회 2013 METALS AND MATERIALS International Vol.19 No.3

One of the most important issues in future Cu-based interconnects is to suppress the resistivity increase in the Cu interconnect line while decreasing the line width below 30 nm. For the purpose of mitigating the resistivity increase in the nanoscale Cu line, alloying Cu with traces of other elements is investigated. The formation of a Cu alloy layer using chemical vapor deposition or electroplating has been rarely studied because of the difficulty in forming Cu alloys with elements such as Al. In this work, Cu-Al alloy films were successfully formed after thermal annealing of Cu/Al multilayers deposited by cyclic metal-organic chemical vapor deposition (C-MOCVD). After the C-MOCVD of Cu/Al multilayers without gas phase reaction between the Cu and Al precursors in the reactor, thermal annealing was used to form Cu-Al alloy films with a small Al content fraction. The resistivity of the alloy films was dependent on the Al precursor delivery time and was lower than that of the aluminum-free Cu film. No presence of intermetallic compounds were detected in the alloy films by X-ray diffraction measurements and transmission electron spectroscopy.

무선 ECG 센서와 안드로이드 앱을 이용한 부정맥 진단 및 치료 시스템 구현에 관한 연구

김남영(Namyoung Kim),기재홍(Jaehong Key) 대한전기학회 2016 정보 및 제어 심포지엄 논문집 Vol.2016 No.4

부정맥은 현대인에게 빈번히 발생하는 질환 중 하나이다. 부정맥의 종류는 일시적으로 발생하였다가 자연스럽게 치유되는 경미한 부정맥 증상으로부터 발생하면 신체에 심각한 손상이나 돌연사로 이어질 수 있는 위협적인 부정맥 질환까지 매우 다양하다. 특히 심장질환과 관련하여 지속적인 모니터링과 치료가 요구되는 부정맥 증상으로는 심실빈맥(ventricular tachycardia, VT), 심방세동 (atrial fibrillation, AF), 심실세동(ventricular fibrillation, VF)등이 있으며, 이러한 증상은 심장 기능의 이상과 직접적인 관련이 있는 것으로 보고되어있고, 방치 시 인체에 치명적일 수 있어 조기 진단과 효과적인 치료가 요구된다. 따라서 본 논문에서는 이러한 생명에 영향을 줄 수 있는 심각한 부정맥 질환에 대한 지속적인 모니터링과 효과적인 치료를 손쉽게 수행할 수 있는 부정맥 진단 및 치료 시스템 구현에 관한 연구 내용을 보고한다. 본 연구에서는 부정맥의 지속적인 모니터링과 조기 진단을 위해서 무선 ECG (electrocardiogram) 센서를 사용하였고, ECG 신호에 대한 신호처리 (signal processing) 기술을 이용한 알고리즘 개발과 이를 연동하여 경고 신호를 의사에게 전송할 수 있는 안드로이드 앱을 개발하였다. 이러한 시스템 구축은 부정맥을 장시간 모니터링 하는 것이 가능하며, 의사에게 부정맥 탐지에 대한 보조적 가이드라인을 제공함으로써 증상에 대한 조기 진단과 효과적인 치료를 가능하게 하도록 하는 것을 목표로 한다. 무선 센서를 통하여 획득되는 심전도 신호는 R-R Peak, QRS Wave의 주파수 특성과 P wave, T wave 탐지 요소를 연산하여 심실빈맥, 심실세동, 심방세동을 효과적으로 탐지하도록 구축하였으며, 안드로이드 앱으로의 최적화 전송을 위하여 지속적으로 발전시키고 있다. 향후 연구 계획으로는 이러한 시스템이 의사의 안드로이드 앱을 통한 원격처방 시스템과 연동하여 원격 조정 (remote control)을 통한 약물 치료도 가능한 진단 및 치료 시스템을 구축할 계획이다.

무선 ECG 센서와 안드로이드 앱을 이용한 부정맥 진단 및 치료 시스템 구현에 관한 연구

김남영(Namyoung Kim),기재홍(Jaehong Key) 대한전자공학회 2016 대한전자공학회 학술대회 Vol.2016 No.4

부정맥은 현대인에게 빈번히 발생하는 질환 중 하나이다. 부정맥의 종류는 일시적으로 발생하였다가 자연스럽게 치유되는 경미한 부정맥 증상으로부터 발생하면 신체에 심각한 손상이나 돌연사로 이어질 수 있는 위협적인 부정맥 질환까지 매우 다양하다. 특히 심장질환과 관련하여 지속적인 모니터링과 치료가 요구되는 부정맥 증상으로는 심실빈맥(ventricular tachycardia, VT), 심방세동 (atrial fibrillation, AF), 심실세동(ventricular fibrillation, VF)등이 있으며, 이러한 증상은 심장 기능의 이상과 직접적인 관련이 있는 것으로 보고되어있고, 방치 시 인체에 치명적일 수 있어 조기 진단과 효과적인 치료가 요구된다. 따라서 본 논문에서는 이러한 생명에 영향을 줄 수 있는 심각한 부정맥 질환에 대한 지속적인 모니터링과 효과적인 치료를 손쉽게 수행할 수 있는 부정맥 진단 및 치료 시스템 구현에 관한 연구 내용을 보고한다. 본 연구에서는 부정맥의 지속적인 모니터링과 조기 진단을 위해서 무선 ECG (electrocardiogram) 센서를 사용하였고, ECG 신호에 대한 신호처리 (signal processing) 기술을 이용한 알고리즘 개발과 이를 연동하여 경고 신호를 의사에게 전송할 수 있는 안드로이드 앱을 개발하였다. 이러한 시스템 구축은 부정맥을 장시간 모니터링 하는 것이 가능하며, 의사에게 부정맥 탐지에 대한 보조적 가이드라인을 제공함으로써 증상에 대한 조기 진단과 효과적인 치료를 가능하게 하도록 하는 것을 목표로 한다. 무선 센서를 통하여 획득되는 심전도 신호는 R-R Peak, QRS Wave의 주파수 특성과 P wave, T wave 탐지 요소를 연산하여 심실빈맥, 심실세동, 심방세동을 효과적으로 탐지하도록 구축하였으며, 안드로이드 앱으로의 최적화 전송을 위하여 지속적으로 발전시키고 있다. 향후 연구 계획으로는 이러한 시스템이 의사의 안드로이드 앱을 통한 원격처방 시스템과 연동하여 원격 조정 (remote control)을 통한 약물 치료도 가능한 진단 및 치료 시스템을 구축할 계획이다.[1]

Synthesis of Multifunctional Magnetic NanoFlakes for Magnetic Resonance Imaging, Hyperthermia, and Targeting.

Cervadoro, Antonio,Cho, Minjung,Key, Jaehong,Cooper, Christy,Stigliano, Cinzia,Aryal, Santosh,Brazdeikis, Audrius,Leary, James F.,Decuzzi, Paolo American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.15

<P/><P>Iron oxide nanoparticles (IOs) are intrinsically theranostic agents that could be used for magnetic resonance imaging (MRI) and local hyperthermia or tissue thermal ablation. Yet, effective hyperthermia and high MR contrast have not been demonstrated within the same nanoparticle configuration. Here, magnetic nanoconstructs are obtained by confining multiple, ∼ 20 nm nanocubes (NCs) within a deoxy-chitosan core. The resulting nanoconstructs—magnetic nanoflakes (MNFs)—exhibit a hydrodynamic diameter of 156 ± 3.6 nm, with a polydispersity index of ∼0.2, and are stable in PBS up to 7 days. Upon exposure to an alternating magnetic field of 512 kHz and 10 kA m<SUP>–1</SUP>, MNFs provide a specific absorption rate (SAR) of ∼75 W g<SUB>Fe</SUB><SUP>–1</SUP>, which is 4–15 times larger than that measured for conventional IOs. Moreover, the same nanoconstructs provide a remarkably high transverse relaxivity of ∼500 (mM s)<SUP>−1</SUP>, at 1.41T. MNFs represent a first step toward the realization of nanoconstructs with superior relaxometric and ablation properties for more effective theranostics.</P>

Auto-Pattern Recognition for Diagnosis in Benign Paroxysmal Positional Vertigo Using Principal Component Analysis: A Preliminary Study

O-Hyeon Gwon,Tae Hoon Kong,Jaehong Key,Sejung Yang,Young Joon Seo 대한평형의학회 2022 Research in Vestibular Science Vol.21 No.1

Objectives: The aim of this study was to develop a filtering algorithm for raw nystagmus images and a diagnostic assistive algorithm using a principal component analysis (PCA) to distinguish the different types of benign paroxysmal positional vertigo (BPPV). Methods: Fifteen video clips of clinical data with typical nystagmus patterns of BPPV (13 cases) and with normal nystamgmus (two cases) were preprocessed when applied the thresholding, morphology operation, residual noise filtering, and center point extraction stages. We analyzed multiple data clusters in a single frame via a PCA; in addition, we statistically analyzed the horizontal and vertical com-ponents of the main vector among the multiple data clusters in the canalolithiasis of the lateral semicircular canal (LSCC) and the posterior semicircular canal (PSCC). Results: We obtained a clear imaginary pupil and data on the fast phases and slow phases after preprocessing the images. For a normal patient, a round shape of clustered dots was observed. Patients with LSCC showed an elongated hori-zontal shape, whereas patients with PSCC showed an oval shape at the (x, y) coordinates. The scalar values (mm) of the horizontal component of the main vector when performing a PCA between the LSCC- and PSCC-BPPV were sub-stantially different (102.08±20.11 vs. 32.36±12.52 mm, respectively; p=0.0012). Additionally, the salar ratio of horizontal to vertical components in LSCC and PSCC exhibited a significant difference (16.11±10.74 mm vs. 2.61±1.07 mm, respectively; p=0.0023). Conclusions: The data of a white simulated imaginary pupil without any back-ground noise can be a separate monitoring option, which can aid clinicians in determining the types of BPPV exhibited. Therefore, this analysis algorithm will provide assistive information for diagnosis of BPPV to clinicians.

암 진단 및 치료용 디스크 나노 입자의 향상된 입자 생산법에 관한 연구

배장열,오은설,이현,기재홍,BAE, J.Y.,OH, E.S.,LEE, H.,KEY, Jaehong 대한의용생체공학회 2016 의공학회지 Vol.37 No.1

나노 입자는 암의 조기 진단과 효과적인 치유를 위한 약물 전달체 또는 영상 조영제로 연구개발 되어왔다. 이러한 나노 입자는 주로 EPR effect로 인해 효과적으로 암 세포를 표적하는 것이 가능하다고 보고되었고, 주로 구형의 나노 입자들이 이러한 실험에 적용되었다. 그러나 최근 EPR effect가 사람의 암 치료에 있어서는 큰 효과를 나타내지 않는다는 한계점이 여러 연구를 통해 제시되고 있다. 따라서 본 연구에서는 이러한 구형 나노 입자의 한계점을 극복하기 위한 새로운 형태의 디스크 나노 입자를 제안하고, 디스크 나노 입자의 생산 과정과 입자의 질을 향상시키기 위한 입자 생산방법에 관한 연구 내용을 보고하였다. 본 연구를 통해 생산된 디스크 나노 입자는 인간 유방암인 MCF7 세포에 적용하여 항암제 전달체로써의 가능성을 평가하였다. Nanoparticles have been studied as therapeutic and imaging agents for the early detection and cure of cancer, Cancer Theranostics. Nanoparticles were considered to effectively target cancer cells due to Enhanced Permeability and Retention (EPR) effect and most nanoparticles have been evaluated by using spherical shapes. However, the problem that the EPR effect is not so effective for human cancer therapy was recently brought up. Therefore, in this study, we suggest novel discoidal nanoparticles to overcome this problem, focusing on their manufacturing process and quality control. Herein, we demonstrate the improved manufacturing method of discoidal nanoparticles and their potential to apply to MCF 7, human breast cancer treatment.

Engineered iron oxide nanoparticles to improve regenerative effects of mesenchymal stem cells

Wan Su Yun,Susmita Aryal,Ye Ji Ahn,서영준,Jaehong Key 대한의용생체공학회 2020 Biomedical Engineering Letters (BMEL) Vol.10 No.2

Mesenchymal stem cells (MSCs) based therapies are a major fi eld of regenerative medicine. However, the success of MSCtherapy relies on the effi ciency of its delivery and retention, diff erentiation, and secreting paracrine factors at the targetsites. Recent studies show that superparamagnetic iron oxide nanoparticles (SPIONs) modulate the regenerative eff ects ofMSCs. After interacting with the cell membrane of MSCs, SPIONs can enter the cells via the endocytic pathway. The physicochemicalproperties of nanoparticles, including size, surface charge (zeta-potential), and surface ligand, infl uence theirinteractions with MSC, such as cellular uptake, cytotoxicity, homing factors, and regenerative related factors (VEGF, TGF-β1). Therefore, in-depth knowledge of the physicochemical properties of SPIONs might be a promising lead in regenerativeand anti-infl ammation research using SPIONs mediated MSCs. In this review, recent research on SPIONs with MSCs andthe various designs of SPIONs are examined and summarized.