Lipid Based Self Assembled Materials Synthesis and Characterization
脂质自组装材料的合成与表征
基本信息
- 批准号:10490411
- 负责人:
- 金额:$ 27.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-17 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffinityAnti-Inflammatory AgentsApolipoprotein A-IBindingBiologicalBiological ProcessBiological ProductsCaliberCell modelCellsChemicalsChemistryCholecalciferolCholesterolClinicCollaborationsCreamDataDevelopmentDrug Delivery SystemsEpithelialEpithelial CellsExposure toEyeEye InjuriesEyedropsFormulationGenerationsGoalsGoldHigh Density LipoproteinsHydrogen BondingHydrophobicityImaging TechniquesImmuneInflammationInflammatoryInfrastructureInjuryInnate Immune SystemLibrariesLipidsLocationMechlorethamineMethodsMicroRNAsMustardMustard GasNucleic AcidsPathway interactionsPeptidesPharmaceutical PreparationsPhospholipidsProcessPropertyProteinsSerumSkinSkin injurySmall Interfering RNASolidSterolsStructureSurfaceTechnologyTherapeuticTopical applicationTranslationsUniversitiesVitamin DWorkarmbasecell typecellular imagingdrug release profileflexibilityhealinghydrophilicityimmune system functionin vivoin vivo evaluationkeratinocytekeratinocyte differentiationlipid metabolismnanoGoldnanoparticlenanotherapeuticnovelnovel therapeuticsreceptorscaffoldscavenger receptorscreeningself assemblysevere injurysmall moleculetargeted treatmentuptakewound healing
项目摘要
SUMMARY
The overall goal of the Lipid-Based Self-Assembled Materials and Characterization Core (LBSAMCC) is to
synthesize, characterize, and deliver highly novel therapeutics for ameliorating the devastating effects of nitrogen
and sulfur mustards to the eye (Project 1) and skin (Project 2). High-density lipoproteins (HDL) are small
nanoparticles that solubilize and transport cholesterol and lipids, are integral in modulating the innate immune
system, and function to enhance the integrity of epithelial barriers. The development and delivery of novel
materials that mimic these key functional features of HDLs and, importantly, enable targeting of appropriate cell
types (e.g. innate immune cells, keratocytes, and keratinocytes) in the eye and skin, highly differentiate this
platform from others to ameliorate injuries caused by mustards. The Thaxton lab pioneered the synthesis of
HDL-like synthetic biologics (HDL NPs) with an inert, solid core gold nanoparticle (AuNP) upon which the self-
assembly of lipid and protein cargos of HDLs can chemically attach. The overall size and surface chemistry can
be strictly controlled to resemble native HDLs enabling these first-generation materials to be tailorable, such that
any number of phospholipids, sterols, and/ or small molecule drugs (e.g. siRNA or microRNA) may be added.
Recent collaborations between the Thaxton and Nguyen labs further demonstrated that the AuNP of first-
generation materials can be swapped out for size-controlling organic core (oc) scaffolds, which can be used to
control biological function (e.g. cholesterol uptake and anti-inflammatory) and opens up the opportunity to load
and unload the core of these targeted materials with relevant therapies (e.g. vitamin D). Ultimately, synthetic
HDL biologics offer a tremendous opportunity for developing novel therapies against eye and/or skin injuries that
occur due to exposure to mustards. The LBSAMCC will be directly responsible for synthesizing a suite of organic
cores (Specific Aim 1) to be used as templates to produce a library of ocHDL NPs with and without small-
molecule and lipid-conjugated drugs and formulated to be topically applied to the eye and skin (Specific Aim 2).
Furthermore, the LBSAMCC will facilitate the complete physicochemical and functional screening of the ocHDL
NPs (Specific Aim 3) so that they can be confidently delivered and further developed in each of the Projects. As
such, the LBSAMCC will deliver effective ocHDL NPs to remediate chemical mustard injuries to the eye and
skin. The impact of this work is that a rigorous approach and step-wise method will produce effective topically
delivered therapies for ameliorating the devastating injuries caused to the eye and skin by nitrogen and sulfur
mustard.
总结
脂质基自组装材料和表征核心(LBSAMCC)的总体目标是
合成、表征和提供用于改善氮的破坏性作用的高度新颖的治疗剂
和硫磺对眼睛(项目1)和皮肤(项目2)的刺激。高密度脂蛋白(HDL)很小
溶解和转运胆固醇和脂质的纳米颗粒是调节先天免疫不可或缺的一部分
系统和功能,以提高上皮屏障的完整性。小说的发展和交付
模拟HDL的这些关键功能特征的材料,重要的是,能够靶向适当的细胞,
眼睛和皮肤中的免疫细胞类型(例如先天免疫细胞、角质形成细胞和角质形成细胞)高度区分这一点。
从其他人的平台,以减轻伤害造成的暴力。萨克斯顿实验室率先合成了
HDL样合成生物制剂(HDL NPs),其具有惰性的固体核金纳米颗粒(AuNP),在其上自
HDL的脂质和蛋白质货物的组装可以化学附着。整体尺寸和表面化学性质可以
严格控制,使其类似于天然HDL,从而使这些第一代材料能够定制,
可以加入任何数量的磷脂、甾醇和/或小分子药物(例如siRNA或microRNA)。
Thaxton和Nguyen实验室之间的最近合作进一步证明,第一代的AuNP-
可以用尺寸控制的有机核心(OC)支架替换生成材料,
控制生物功能(例如胆固醇摄取和抗炎),并打开加载的机会
并通过相关疗法(例如维生素D)卸载这些靶向物质的核心。最终,
HDL生物制剂为开发针对眼睛和/或皮肤损伤的新疗法提供了巨大的机会,
是由于暴露在辐射下而发生的。LBSAMCC将直接负责合成一套有机化合物,
核心(具体目标1)用作模板以产生具有和不具有小-
分子和脂质缀合的药物,并配制成局部应用于眼睛和皮肤(特定目的2)。
此外,LBSAMCC将有助于对ocHDL进行完整的理化和功能筛选
NP(具体目标3),以便在每个项目中自信地交付和进一步发展。作为
因此,LBSAMCC将递送有效的ocHDL NP以修复对眼睛的化学芥子气损伤,
皮肤这项工作的影响是,严格的方法和逐步的方法将产生有效的局部
用于改善氮和硫对眼睛和皮肤造成的破坏性损伤的治疗方法
芥末。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Colby Shad Thaxton其他文献
Redox Redux: Nrf2 Mediates Resistance to Ferroptosis and Apoptosis in High Grade B-Cell Lymphoma
- DOI:
10.1182/blood-2024-210592 - 发表时间:
2024-11-05 - 期刊:
- 影响因子:
- 作者:
Meiying Yang;Jonathan S Rink;Adam Yuh Lin;Shuo Yang;Colby Shad Thaxton;Leo I. Gordon - 通讯作者:
Leo I. Gordon
Investigations of Redox Resistance in Aggressive Lymphomas with Cholesterol Modulating Lipid Nanoparticles
- DOI:
10.1182/blood-2022-168394 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Meiying Yang;Jonathan Scott Rink;Shuo Yang;Eva Yang;Kaylin Marie McMahon;Colby Shad Thaxton;Leo I. Gordon;Adam Yuh Lin - 通讯作者:
Adam Yuh Lin
Synthetic Lipid Nanoparticles Actively Target Acute Myeloid Leukemia (AML) Cells and Induce Ferroptosis through Decreased Expression of Glutathione Peroxidase 4
- DOI:
10.1182/blood-2022-168154 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Adam Yuh Lin;Jonathan Scott Rink;Eva Yang;Sara Small;Fransheska Serrano;Yasmin Abaza;Jessica K. Altman;Leonidas C. Platanias;Colby Shad Thaxton;Leo I. Gordon - 通讯作者:
Leo I. Gordon
Receptor Targeted Delivery of the p38γ Inhibitor PIK-75 By Organic-Core Templated Lipid Nanoparticles in Cutaneous T Cell Lymphoma
- DOI:
10.1182/blood-2022-158864 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Jonathan Scott Rink;Stephen E. Henrich;Alexandra Moxley;Xu Hannah Zhang;Xiwei Wu;SonBinh Nguyen;Christiane Querfeld;David A. Horne;Steve T. Rosen;Leo I. Gordon;Colby Shad Thaxton;Adam Yuh Lin - 通讯作者:
Adam Yuh Lin
Colby Shad Thaxton的其他文献
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{{ truncateString('Colby Shad Thaxton', 18)}}的其他基金
Lipid Based Self Assembled Materials Synthesis and Characterization
脂质自组装材料的合成与表征
- 批准号:
10682620 - 财政年份:2021
- 资助金额:
$ 27.52万 - 项目类别:
Lipid Based Self Assembled Materials Synthesis and Characterization
脂质自组装材料的合成与表征
- 批准号:
10282408 - 财政年份:2021
- 资助金额:
$ 27.52万 - 项目类别:
High Density Lipoprotein Nanoparticles for siRNA Delivery
用于 siRNA 递送的高密度脂蛋白纳米颗粒
- 批准号:
8680188 - 财政年份:2012
- 资助金额:
$ 27.52万 - 项目类别:
High Density Lipoprotein Nanoparticles for siRNA Delivery
用于 siRNA 递送的高密度脂蛋白纳米颗粒
- 批准号:
9088367 - 财政年份:2012
- 资助金额:
$ 27.52万 - 项目类别:
High Density Lipoprotein Nanoparticles for siRNA Delivery
用于 siRNA 递送的高密度脂蛋白纳米颗粒
- 批准号:
8549175 - 财政年份:2012
- 资助金额:
$ 27.52万 - 项目类别:
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