Biomimetic Nanosponges to 'Lure and Kill' Phospholipase A2

仿生纳米海绵“引诱并杀死”磷脂酶 A2

基本信息

  • 批准号:
    1904702
  • 负责人:
  • 金额:
    $ 45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-12-15 至 2022-11-30
  • 项目状态:
    已结题

项目摘要

NON-TECHNICAL: This award by the Biomaterials Program in the Division of Materials Research to the University of California, San Diego is to explore a highly innovative strategy for effective inhibition of harmful enzymes and to investigate the fundamental principles of this new approach. The proposal specifically targets phospholipase A2 (PLA2), key players in critical diseases including autoimmune diseases, cancers, and venomous injuries. Although PLA2 inhibition has been shown critical for the treatment of these diseases, safe and effective PLA2 inhibitors remain lacking. Herein, a nanostructure is constructed by using safe polymers and natural cell membranes. They are further functionalized to first 'lure' PLA2 for an attack and then 'kill' the incoming PLA2. The resulting nanoparticles (denoted "lure and kill" and abbreviated 'L&K-NP') combine PLA2 stimulation and inhibition, two seemingly counteracting functions, together for synergistic inhibition of the enzyme. Meanwhile, these nanoparticles preserve the functions of inhibitors and simulants while suppressing their toxicity otherwise unsafe for direct use. L&K-NPs also feature modular and tailorable design, representing a platform anti-PLA2 technology. The proposal will also carry out well-planned education components as an integral part of the project. The outcome is expected to contribute significantly to the continual growth of biomaterials science and engineering. Particular efforts will be dedicated to training a new generation of skilled and collaborative researchers and educators in the field of biomaterials and nanomedicine.TECHNICAL: The research objective of this award is to develop and investigate a novel biomimetic nanoparticle platform with an integrated "lure and kill" mechanism for effective inhibition of phospholipase A2 (PLA2), a class of enzymes responsible for numerous diseases. Specifically, the design leverages nanoparticles coated with natural cell membranes that are susceptible to PLA2 attack. However, instead of being a simple sacrificial approach against PLA2, the proposed design incorporates two additional components: PLA2 stimulants such as melittin that spontaneously insert into the membrane and 'lure' the enzyme for an attack, and PLA2 inhibitors with a lipid-like structure that, upon membrane digestion, expose themselves to 'kill' PLA2. The resulting nanoparticles (denoted L&K-NPs) incorporate both PLA2 stimulants and inhibitors within the cell membrane, therefore eliminating the toxicity associated with free molecules of the stimulants and inhibitors for safe use. To achieve the primary goal, three specific research tasks will be pursued: (1) fabricate and optimize L&K-NP formulation, (2) validate L&K-NPs for preventing cell damage from venomous PLA2, and (3) extend L&K-NPs to inhibit mammalian PLA2 by using macrophage membrane coating. Furthermore, through this project, the PI will train a team of interdisciplinary and multi-level collaborative young investigators, provide minority students with stimulating research experience, and enhance scientific education among K-12 students and community at large.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
非技术性:该奖项由加州大学圣地亚哥分校材料研究部生物材料项目授予,旨在探索有效抑制有害酶的高度创新策略,并研究这种新方法的基本原理。该提案专门针对磷脂酶A2(PLA 2),这是包括自身免疫性疾病,癌症和有毒伤害在内的关键疾病的关键参与者。虽然PLA 2抑制已被证明是治疗这些疾病的关键,但仍然缺乏安全有效的PLA 2抑制剂。在此,通过使用安全的聚合物和天然细胞膜来构建纳米结构。它们被进一步功能化以首先“引诱”PLA 2进行攻击,然后“杀死”进入的PLA 2。所得的纳米颗粒(表示为“引诱和杀死”,缩写为“L K-NP”)将联合收割机PLA 2刺激和抑制(两种看似相互抵消的功能)结合在一起,以协同抑制酶。同时,这些纳米颗粒保留了抑制剂和模拟物的功能,同时抑制了它们的毒性,否则直接使用不安全。L K-NP还具有模块化和可定制的设计,代表了平台抗PLA 2技术。该提案还将实施精心规划的教育部分,作为项目的一个组成部分。该成果有望为生物材料科学与工程的持续发展做出重大贡献。该奖项的研究目标是开发和研究一种新型的仿生纳米颗粒平台,该平台具有一种集成的“引诱和杀死”机制,可有效抑制磷脂酶A2(PLA 2),这是一种负责许多疾病的酶。具体来说,该设计利用了涂覆有易受PLA 2攻击的天然细胞膜的纳米颗粒。然而,所提出的设计不是针对PLA 2的简单牺牲方法,而是结合了两个额外的组分:PLA 2刺激剂,如蜂毒肽,其自发地插入膜中并“引诱”酶进行攻击,以及具有脂质样结构的PLA 2抑制剂,其在膜消化时暴露自身以“杀死”PLA 2。所得纳米颗粒(表示为LK-NP)将PLA 2刺激剂和抑制剂两者并入细胞膜内,因此消除了与刺激剂和抑制剂的游离分子相关的毒性以供安全使用。为了实现主要目标,将进行三个具体的研究任务:(1)制备和优化L K-NP制剂,(2)验证L K-NP用于预防有毒PLA 2的细胞损伤,以及(3)通过使用巨噬细胞膜涂层来扩展L K-NP以抑制哺乳动物PLA 2。此外,通过该项目,PI将培养一支跨学科和多层次合作的年轻研究人员团队,为少数民族学生提供激励性的研究经验,并加强K-12学生和整个社区的科学教育。该奖项反映了NSF的法定使命,并通过使用基金会的智力价值和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction
  • DOI:
    10.1186/s13059-020-02145-6
  • 发表时间:
    2020-09-10
  • 期刊:
  • 影响因子:
    12.3
  • 作者:
    Huang, Norman;Fan, Xiaochen;Zhong, Sheng
  • 通讯作者:
    Zhong, Sheng
Nanomaterial Biointerfacing via Mitochondrial Membrane Coating for Targeted Detoxification and Molecular Detection
  • DOI:
    10.1021/acs.nanolett.1c00238
  • 发表时间:
    2021-03-09
  • 期刊:
  • 影响因子:
    10.8
  • 作者:
    Gong, Hua;Zhang, Qiangzhe;Zhang, Liangfang
  • 通讯作者:
    Zhang, Liangfang
Recent Progress in Capturing and Neutralizing Inflammatory Cytokines
捕获和中和炎症细胞因子的最新进展
  • DOI:
    10.31635/ccschem.020.202000165
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    11.2
  • 作者:
    Zhang, Qiangzhe;Gong, Hua;Gao, Weiwei;Zhang, Liangfang
  • 通讯作者:
    Zhang, Liangfang
ACE2 Receptor-Modified Algae-Based Microrobot for Removal of SARS-CoV-2 in Wastewater
  • DOI:
    10.1021/jacs.1c04933
  • 发表时间:
    2021-07
  • 期刊:
  • 影响因子:
    15
  • 作者:
    Fangyu Zhang;Zhengxing Li;Lu Yin;Qiangzhe Zhang;Nelly Askarinam;Rodolfo Mundaca-Uribe;Farshad Tehrani;Emil Karshalev;Weiwei Gao;Liangfang Zhang;Joseph Wang
  • 通讯作者:
    Fangyu Zhang;Zhengxing Li;Lu Yin;Qiangzhe Zhang;Nelly Askarinam;Rodolfo Mundaca-Uribe;Farshad Tehrani;Emil Karshalev;Weiwei Gao;Liangfang Zhang;Joseph Wang
Biomembrane‐Functionalized Micromotors: Biocompatible Active Devices for Diverse Biomedical Applications
生物膜——功能化微电机:用于多种生物医学应用的生物相容性有源器件
  • DOI:
    10.1002/adma.202107177
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    29.4
  • 作者:
    Zhang, Fangyu;Mundaca‐Uribe, Rodolfo;Askarinam, Nelly;Li, Zhengxing;Gao, Weiwei;Zhang, Liangfang;Wang, Joseph
  • 通讯作者:
    Wang, Joseph
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Liangfang Zhang其他文献

Lipid–Polymer Nanomaterials
脂质聚合物纳米材料
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Corbin Clawson;S. Esener;Liangfang Zhang
  • 通讯作者:
    Liangfang Zhang
NOVEL SYNTHESIS OF POLYMERIC NANOPARTICLES FOR DRUG DELIVERY APPLICATIONS USING MICROFLUIDIC RAPID MIXING
使用微流体快速混合的药物输送应用的聚合物纳米颗粒的新型合成
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    P. Basto;F. Gu;Liangfang Zhang;C. Cannizzaro;R. Langer;O. Farokhzad;R. Karnik
  • 通讯作者:
    R. Karnik
Synthesis of Erythrocyte Nanodiscs for Bacterial Toxin Neutralization.
用于细菌毒素中和的红细胞纳米盘的合成。
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Lei Sun;Dan Wang;Ilkoo Noh;Ronnie H. Fang;Weiwei Gao;Liangfang Zhang
  • 通讯作者:
    Liangfang Zhang
Corrigendum: Lens regeneration using endogenous stem cells with gain of visual function
勘误表:使用内源干细胞进行晶状体再生并获得视觉功能
  • DOI:
    10.1038/nature19831
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    64.8
  • 作者:
    Haotian Lin;Ouyang Hong;Jie Zhu;Shan‐Zhou Huang;Zhenzhen Liu;Shuyi Chen;Guiqun Cao;Gen Li;Robert A J Signer;Yanxin Xu;Christopher Chung;Ying Zhang;Danni Lin;Sherrina H. Patel;Frances Wu;Huimin Cai;Jiayi Hou;Cindy Wen;Maryam Jafari;Xialin Liu;L. Luo;Jin Zhu;Austin Qiu;Rui Hou;Baoxin Chen;Jiangna Chen;D. Granet;C. Heichel;F. Shang;Xuri Li;M. Krawczyk;D. Skowronska;Yujuan Wang;W. Shi;Daniel Chen;Zheng Zhong;Sheng Zhong;Liangfang Zhang;Shaochen Chen;S. Morrison;R. Maas;Kang Zhang;Yizhi Liu
  • 通讯作者:
    Yizhi Liu
Optical detection of abnormal skin scarring
异常皮肤疤痕的光学检测
  • DOI:
    10.1038/s41551-018-0222-1
  • 发表时间:
    2018
  • 期刊:
  • 影响因子:
    28.1
  • 作者:
    Ronnie H. Fang;Liangfang Zhang
  • 通讯作者:
    Liangfang Zhang

Liangfang Zhang的其他文献

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{{ truncateString('Liangfang Zhang', 18)}}的其他基金

Macrophage Membrane-Coated Nanoparticles for Endotoxin Neutralization
用于中和内毒素的巨噬细胞膜包被的纳米颗粒
  • 批准号:
    1505699
  • 财政年份:
    2015
  • 资助金额:
    $ 45万
  • 项目类别:
    Continuing Grant
EAGER: Red Blood Cell Membrane Camouflaged Nanoparticles for Drug Delivery
EAGER:用于药物输送的红细胞膜伪装纳米颗粒
  • 批准号:
    1216461
  • 财政年份:
    2012
  • 资助金额:
    $ 45万
  • 项目类别:
    Continuing Grant
Systematic Approaches to Scale-up of Biocompatible Drug Delivery Nanoparticles for High-Rate Production
放大生物相容性药物输送纳米颗粒以实现高产量的系统方法
  • 批准号:
    1031239
  • 财政年份:
    2010
  • 资助金额:
    $ 45万
  • 项目类别:
    Standard Grant

相似海外基金

Biomimetic Macrophage Membrane-Coated Nanosponges: A Novel Therapeutic for Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Hospital-Associated Pneumonia
仿生巨噬细胞膜包被的纳米海绵:一种治疗多重耐药铜绿假单胞菌和鲍曼不动杆菌医院相关肺炎的新疗法
  • 批准号:
    10674406
  • 财政年份:
    2023
  • 资助金额:
    $ 45万
  • 项目类别:
Engineering nanosponges to sequester bacterial exotoxins for protection against severe infection
工程纳米海绵可隔离细菌外毒素以防止严重感染
  • 批准号:
    2889873
  • 财政年份:
    2023
  • 资助金额:
    $ 45万
  • 项目类别:
    Studentship
NarcoBond: Opioid Targeted Biomimetic Nanosponges for Treatment of Opioid Overdose
NarcoBond:阿片类药物靶向仿生纳米海绵用于治疗阿片类药物过量
  • 批准号:
    9912595
  • 财政年份:
    2019
  • 资助金额:
    $ 45万
  • 项目类别:
NarcoBond: Opioid Targeted Biomimetic Nanosponges for Treatment of Opioid Overdose
NarcoBond:阿片类药物靶向仿生纳米海绵用于治疗阿片类药物过量
  • 批准号:
    10179237
  • 财政年份:
    2019
  • 资助金额:
    $ 45万
  • 项目类别:
Crosslinked Nanosponges for the Topical Treatment of Wound Biofilms
用于局部治疗伤口生物膜的交联纳米海绵
  • 批准号:
    10189492
  • 财政年份:
    2018
  • 资助金额:
    $ 45万
  • 项目类别:
SBIR Phase I: Development of Biomimetic Toxin Nanosponges with Enhanced Toxin Affinity
SBIR 第一阶段:开发具有增强毒素亲和力的仿生毒素纳米海绵
  • 批准号:
    1345715
  • 财政年份:
    2014
  • 资助金额:
    $ 45万
  • 项目类别:
    Standard Grant
Protein/Peptide Separation with Polymer Brush Nanosponges
使用聚合物刷纳米海绵分离蛋白质/肽
  • 批准号:
    7366938
  • 财政年份:
    2008
  • 资助金额:
    $ 45万
  • 项目类别:
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