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RISS 인기검색어
- 검색키워드
- 저자 : Yoshitaka J. Sei (검색결과 3 건)
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Detecting the functional complexities between high-density lipoprotein mimetics
Sei, Yoshitaka J.,Ahn, Jungho,Kim, Taeyoung,Shin, Eunjung,Santiago-Lopez, Angel J.,Jang, Seung Soon,Jeon, Noo Li,Jang, Young C.,Kim, YongTae Elsevier 2018 Biomaterials Vol.170 No.-
<P><B>Abstract</B></P> <P>High-density lipoprotein (HDL) is a key regulator of lipid homeostasis through its native roles like reverse cholesterol transport. The reconstitution of this natural nanoparticle (NP) has become a nexus between nanomedicine and multi-disease therapies, for which a major portion of HDL functionality is attributed to its primary scaffolding protein, apolipoprotein A1 (apoA1). ApoA1-mimetic peptides were formulated as cost-effective alternatives to apoA1-based therapies; reverse-4F (r4F) is one such peptide used as part of a nanoparticle platform. While similarities between r4F- and apoA1-based HDL-mimetic nanoparticles have been identified, key functional differences native to HDL have remained undetected. In the present study, we executed a multidisciplinary approach to uncover these differences by exploring the form, function, and medical applicability of engineered HDL-mimetic NPs (eHNPs) made from r4F (eHNP-r4F) and from apoA1 (eHNP-A1). Comparative analyses of the eHNPs through computational molecular dynamics (MD), advanced microfluidic NP synthesis and screening technologies, and <I>in vivo</I> animal model studies extracted distinguishable eHNP characteristics: the eHNPs share identical structural and compositional characteristics with distinct differences in NP stability and organization; eHNP-A1 could more significantly stimulate anti-inflammatory responses characteristic of the scavenger receptor class B type 1 (SR-B1) mediated pathways; and eHNP-A1 could outperform eHNP-r4F in the delivery of a model hydrophobic drug to an <I>in vivo</I> tumor. The biomimetic microfluidic technologies and MD simulations uniquely enabled our comparative analysis through which we determined that while eHNP-r4F is a capable NP with properties mimicking natural eHNP-A1, challenges remain in reconstituting the full functionality of NPs naturally derived from humans.</P>
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Ahn, Jungho,Sei, Yoshitaka J.,Jeon, Noo Li,Kim, YongTae IEEE 2018 IEEE TRANSACTIONS ON NANOTECHNOLOGY Vol. No.
<P>High-density lipoproteins (HDL) are known to contribute to vascular homeostasis, but recent HDL-mimetic therapies attempting to capitalize on the vasculoprotective properties associated with HDL have been met with roadblocks in their translational journey to the clinic largely due to the complex role of HDL in vasculature. Among the adaptive processes seen in vasculature, angiogenesis is one process that is both crucial to vascular remodeling and is dependent on HDL to an unknown extent. Here we investigate the effect of HDL mimetic nanoparticles on the angiogenic process of sprouting using a microengineered three-dimensional vascular system. Our study reveals critical effects of HDL mimetic nanoparticles on angiogenesis: 1) exhibiting a bi-phasic effect on angiogenic sprout growth and 2) inhibiting TNF-<I>α</I> stimulated angiogenesis. This method demonstrates the feasibility of leveraging a microengineered physiological model to screen the effects of bioinspired nanoparticles as part of a foundational study for accelerating translational research through biomimetic technologies.</P>
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