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Nanomedicine approaches for medulloblastoma therapy
Lim Chaemin,Koo Jain,오경택 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.2
Background Over the past 30 years, brain tumors have been intensively studied with a variety of therapeutic approaches. However, brain cancer is still one of the most lethal forms of cancer, and the mortality rates have still not significantly improved. Since the late 2010s, transcriptomic analysis of medulloblastoma (MB), the most malignant pediatric brain tumor, has been actively conducted. These efforts have facilitated classification of MB into specific subgroups, enabling more molecularly targeted therapies. However, from a pharmaceutical standpoint, there is one more hurdle to overcome, which is the blood-brain barrier (BBB). Area Covered In this review, we provide information on the characteristics of each subgroup of MB and a list of Food and Drug Administration (FDA)-approved drugs or drugs in clinical trials used for the treatment of this disease. In addition, we introduce lists of methods that can overcome the BBB, a major hurdle for MB treatment, by applying nanotechnology. Finally, we provide a general overview of the state of nanomedicine for brain tumors. Expert Opinion Various types of nanotechnologies have been extensively studied and have shown clear advantages for treatment of brain tumors. However, despite the exploration of these various nanoparticles in preclinical studies, the types of nanoparticles evaluated in clinical trials are very limited, and a number of clinical trial failures have also occurred. Therefore, further insights into relevant regulations as well as rational design of nanoparticles for improved reproducibility are required to bridge the gap between preclinical and clinical studies.
A stable nanoplatform for antitumor activity using PEG-PLL-PLA triblock co-polyelectrolyte
Lim, Chaemin,Sim, Taehoon,Hoang, Ngoc Ha,Oh, Kyung Taek Elsevier 2017 Colloids and Surfaces B Vol.153 No.-
<P><B>Abstract</B></P> <P>Polyelectrolyte has been proposed as an efficient approach for various types of drug formulations. However, one drawback of using the conventional polyelectrolyte for drug delivery is its dissociation in <I>in vivo</I> conditions by counter ions due to the lack of self-assembling aggregation force. In this study, we reported a stable nanoplatform based on triblock co-polyelectrolyte composed of a poly(ethylene glycol), poly(<SMALL>L</SMALL>-lysine), and poly(lactic acid). These co-polyelectrolytes formed stable aggregates through the hydrophobic interaction of PLA and showed consistent particle sizes under a high salt concentration. In addition, the doxorubicin (Dox) loaded triblock co-polyelectrolyte demonstrated enhanced cellular uptake and drug cytotoxicity with a positive charge from the poly(<SMALL>L</SMALL>-lysine) layer. <I>In vivo</I>, the triblock aggregates exhibited intensive accumulation at the targeted tumor site for 24h with good antitumor therapeutic efficacy. Therefore, the prepared stable triblock co-polyelectrolyte may have considerable potential as a nanomedicinal platform for anticancer and multi-drug combination therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A stable multilayer nanoplatform from PEG-PLL-PLA was developed. </LI> <LI> The Dox loaded nanoplatform showed higher cellular uptake in tumor cells. </LI> <LI> The Dox loaded nanoplatform was accumulated into tumor sites in vivo. </LI> <LI> The Dox loaded nanoplatform showed higher efficacy than Dox-HCl. </LI> <LI> The nanoplatform demonstrated the feasibility of multi drug delivery. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
A charge-reversible nanocarrier using PEG-PLL (- <i>g</i> -Ce6, DMA)-PLA for photodynamic therapy
Lim, Chaemin,Sim, Taehoon,Hoang, Ngoc Ha,Jung, Chan Eun,Lee, Eun Seong,Youn, Yu Seok,Oh, Kyung Taek Dove Medical Press 2017 International journal of nanomedicine Vol.12 No.-
<P>A polyelectrolyte nanoparticle composed of PEG-PLL(-<I>g</I>-Ce6, DMA)-PLA was developed for nanomedicinal application in photodynamic therapy. These nanoparticles formed stable aggregates through the hydrophobic interaction of poly(lactic acid) and demonstrated pH-dependent behaviors such as surface charge conversion and enhanced cellular uptake at acidic pH, resulting in improved phototoxicity. In vivo animal imaging revealed that the prepared PEG-PLL(-<I>g</I>-Ce6, DMA)-PLA nanoparticles effectively accumulated at the targeted tumor site through enhanced permeability and retention effects. Reversible surface charge for PEG-PLL (-<I>g</I>-Ce6, DMA)-PLA nanoparticles allows the nanoparticles to escape the immune system and concentrate on the tumor tissue. Tumor growth in the nude mice treated with the nanoparticles decreased significantly and the hydrophobic interaction in the poly(lactic acid) block could allow the incorporation of multiple drugs. Therefore, the PEG-PLL(-<I>g</I>-Ce6, DMA)-PLA nanoparticles could have considerable potential as a nanomedicinal platform for photodynamic therapy.</P>
Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers
Lim, Chaemin,Youn, Yu Seok,Lee, Kyung Soo,Hoang, Ngoc Ha,Sim, Taehoon,Lee, Eun Seong,Oh, Kyung Taek Dove Medical Press 2016 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.11 No.-
<P>A polyelectrolyte ionomer complex (PIC) composed of cationic and anionic polymers was developed for nanomedical applications. Here, a poly(ethylene glycol)–poly(lactic acid)–poly(ethylene imine) triblock copolymer (PEG–PLA–PEI) and a poly(aspartic acid) (P[Asp]) homopolymer were synthesized. These polyelectrolytes formed stable aggregates through electrostatic interactions between the cationic PEI and the anionic P(Asp) blocks. In particular, the addition of a hydrophobic PLA and a hydrophilic PEG to triblock copolyelectrolytes provided colloidal aggregation stability by forming a tight hydrophobic core and steric hindrance on the surface of PIC, respectively. The PIC showed different particle sizes and zeta potentials depending on the ratio of cationic PEI and anionic P(Asp) blocks (C/A ratio). The doxorubicin (dox)-loaded PIC, prepared with a C/A ratio of 8, demonstrated pH-dependent behavior by the deprotonation/protonation of polyelectrolyte blocks. The drug release and the cytotoxicity of the dox-loaded PIC (C/A ratio: 8) increased under acidic conditions compared with physiological pH, due to the destabilization of the formation of the electrostatic core. In vivo animal imaging revealed that the prepared PIC accumulated at the targeted tumor site for 24 hours. Therefore, the prepared pH-sensitive PIC could have considerable potential as a nanomedicinal platform for anticancer therapy.</P>
Cyclic RGD-conjugated Pluronic <sup>®</sup> blending system for active, targeted drug delivery
Lim, Chaemin,Moon, Junseong,Sim, Taehoon,Hoang, Ngoc Ha,Won, Woong Roeck,Lee, Eun Seong,Youn, Yu Seok,Choi, Han-Gon,Oh, Kyungsoo,Oh, Kyung Taek Dove Medical Press 2018 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.13 No.-
<P><B>Background</B></P><P>Blending micellar systems of different types of polymers has been proposed as an efficient approach for tailor-made drug formulations. The lamellar structure of hydrophobic polymers may provide a high drug loading capacity, and hydrophilic polymers may provide good colloidal stability.</P><P><B>Methods</B></P><P>In this study, the anticancer model drug docetaxel was loaded onto a nanosized blending micellar system with two pluronics (L121/F127). To achieve increased antitumor activity, the cyclic arginine-glycine-aspartic acid tripeptide (cRGD) as an active tumor targeting ligand was conjugated to the blending system.</P><P><B>Results</B></P><P>The docetaxel-loaded Pluronic blending system exhibited a higher drug loading capacity than that of F127 and showed high colloidal stability with a spherical structure. cRGD conjugates demonstrated enhanced drug cellular uptake and anticancer activity against αvβ3 integrin-overexpressing U87MG cancer cells. In vivo animal imaging also revealed that the prepared cRGD-conjugated nanoparticles effectively accumulated at the targeted tumor site through an active and passive targeting strategy.</P><P><B>Conclusion</B></P><P>Accordingly, the prepared nanosized system shows potential as a tailor-made, active targeting, nanomedicinal platform for anticancer therapy. We believe that this novel nanoplatform will provide insights for advancement of tumor therapy.</P>
초음속 발사체에 발생하는 공력특성에 관한 수치해석적 연구
임채민(Chaemin Lim),김희동(Heuydong Kim),이정민(Jeongmin Lee) 한국유체기계학회 2006 유체기계 연구개발 발표회 논문집 Vol.- No.-
A computational work has been performed to investigate the aerodynamics of a projectile which is launched from a ballistic range. A moving coordinate method for a multi-domain technique is employed to simulate unsteady projectile flows with a moving boundary. The variation of a virtual mass and the shape of projectile are added to the axisymmetric unsteady Euler equation systems. The present computational results properly predict the velocity, acceleration, drag histories and the major flow characteristics of the projectile.
양자화 시뮬레이션 플랫폼의 GUI-기반 통합을 위한 관리 모듈
임채민 ( Chaemin Lim ),조상영 ( Sang-young Cho ),임승호 ( Seung-ho Lim ) 한국정보처리학회 2020 한국정보처리학회 학술대회논문집 Vol.27 No.2
신경망 모델 데이터의 양자화는 모델 크기를 줄이고 추론 시간을 단축할 수 있다. 본 논문에서는 양자화를 지원하는 시뮬레이션 플랫폼의 전체 동작 관리를 위한 관리 모듈에 대해 기술한다. 시뮬레이션 플랫폼이 다중 사용자를 지원하고 다양한 기능을 지원하기 때문에 효율적인 관리 모듈의 구현은 중요하다. 관리 모듈은 웹 서비스의 후위단으로 설계되었으며 라우터와 이벤트 수신자, 프로세스 관리자, 파일 관리자, 세션 관리자, 보조 기능 등을 구현하였다.
Sim, Taehoon,Lim, Chaemin,Hoang, Ngoc Ha,Kim, Jae Eun,Lee, Eun Seong,Youn, Yu Seok,Oh, Kyung Taek Royal Society of Chemistry 2017 Journal of Materials Chemistry B Vol. No.
<P>Poly(aspartic acid-<I>graft</I>-imidazole)-poly(ethylene glycol) (P(Asp-<I>g</I>-Im)-PEG) was utilized as a pH-sensitive nanocarrier of the photosensitizer indole-3-acetic acid (IAA) for the treatment of skin cancer. IAA loaded micelles (ILMs) exhibited the formation of <I>ca.</I> 140 nm spherical particles at pH 7.4. The micelles disintegrated at acidic pHs, resulting in pH-dependent IAA release and cytotoxicity. Treatment of ILMs with visible light at a wavelength of 480 nm caused pH dependent synergistic cell damage in both <I>in vitro</I> and <I>in vivo</I> models using the B16F10 melanoma cell line. Interestingly, ILMs synergistically produced reactive oxygen species (ROS) at an acidic pH of 6.5 with visible light irradiation by proton coupled electron transfer (PCET). The pH sensitive ILMs could be considered a potent nanomedicine used to exert synergistic photodynamic therapeutic effects to treat cancers.</P>