A Fullerene-based Molecular Route towards Designer Nanoparticles
基于富勒烯的设计纳米粒子的分子路线
基本信息
- 批准号:10713377
- 负责人:
- 金额:$ 39.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdoptedBiochemicalBiologicalBiologyBiomedical ResearchCharacteristicsChemicalsCommunitiesContrast MediaDetectionDiagnosticDiffusionDyesEventFluorescent ProbesFullerenesFutureGoalsHeavy MetalsImageLibrariesLigandsMagnetic Resonance ImagingMedicalMicroscopicMolecularNaturePharmaceutical PreparationsPhotobleachingPropertyQuality ControlRNARNA amplificationReactionReproducibilityResearchResistanceRouteSafetySeriesShapesSignal TransductionSpecificitySurfaceSynthesis ChemistryTechnologyTherapeuticWorkcancer cellcovalent bonddesignfluorescence imagingfullerene C60imaging probelive cell imagingnanoparticlenanoprobenext generationnovelparticleratiometricscaffoldscale upsingle-molecule FRETsmall moleculetool
项目摘要
Project Summary
In chemical biology, precise bottom-up synthesis bridging the microscopic and macroscopic world is an
ultimate goal. Recent advancements in nanoparticles have yielded biomedical tools with tailorable properties
and exceptional strength in overcoming the hurdles associated with conventional passive/diffusion-based
diagnostic and therapeutic drugs. However, conventional nanoparticles are inherently polydisperse, and
therefore generally lack the precision and uniformity that are needed for the robust quantification and
reproducibility in biomedical research, and for the quality control in scaling up and long-term storage in future
applications. Fullerenes are nm-sized molecules that would hold their size and shape as a rigid multivalent core
like inorganic particles, and allow for organic reactions to introduce biological properties and functions via robust
C-C covalent bonds. In our group, we utilize a characteristic hexakisadduct of fullerene C60 as a core scaffold
and modular platform to develop a series of precise “molecular nanoparticles” with desirable surface function,
multivalency, and size, for novel magnetic resonance imaging and fluorescence imaging probes. Our work
comprises four conceptually independent, but technically synergistic Research Themes.
In the first Theme, MRI probes with multivalent targeting to cancer cells, we will build on our recently
developed “metallobuckytrio” (MBT), to develop precise molecular nanoparticles with Gd-containing endohedral
metallofullerene and biochemical ligands for next-generation MRI contrast agents. These MRI probes will check
all the “wish list items” in future MRI probes: Gd heavy-metal safety, high relaxivity, structural precision, and
biochemical specificity. In the second Theme, FullerFISH with fast and quantitative signal amplification, we will
synthesize multivalent molecular constructs to amplify RNA-FISH signals with 10-30 dyes, to facilitate the
detection and quantification of short of low-abundance RNA molecules. In the third Theme, signal amplifying and
antioxidative probes for live cell imaging and smFRET imaging, we will exploit the anti-oxidative property and
multivalency of the hexakisadduct fullerene nanoparticles, load them with organic dyes, to develop
photobleaching-resistant and signal-amplifying imaging probes. In the fourth Theme, precise ratiometric
nanoprobes, we will introduce bioresponsive dyes and “always on” reference dyes in accurate 1:1 ratio and exact
colocalization onto the antioxidative, multivalent fullerene nanoparticles to achieve ratiometric imaging for
sensing and tracking biological events.
These four Themes will combine our synthetic expertise to turn C60 into precise molecular nanoparticles with
desirable ligands, with the resourceful library of nanoparticle and small-molecule research, to marry the precision
of molecules and the multivalency and multiplexity of nanoparticles in chemical biology. With the modular nature
of our synthetic platform, we anticipate the proposed technology will be adopted by broader biological
communities with many new bottom-up designs and ligands by choice.
项目总结
项目成果
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