Engineering Next-Generation Nanoparticles One Layer at a Time
一次一层地设计下一代纳米粒子
基本信息
- 批准号:10668497
- 负责人:
- 金额:$ 4.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdsorptionAffectAntibodiesAntineoplastic AgentsArchitectureBindingBiologicalBiological AvailabilityCOVID-19 vaccineCancer ControlCancer ModelCellsCharacteristicsChargeChemistryClinicalCytoplasmDepositionDrug ControlsDrug Delivery SystemsDrug KineticsEffectivenessElectrostaticsEndosomesEngineeringFDA approvedFilmFluorescence Resonance Energy TransferFormulationGoalsHalf-LifeHydrogen BondingImmunotherapeutic agentIn VitroInterleukin-12Ionic StrengthsKineticsKnowledgeLibrariesLiposomesMalignant NeoplasmsMalignant neoplasm of ovaryMediatingMentorsMethodsModelingModernizationModificationMolecular ConformationMonitorNucleic AcidsOncogenesOperative Surgical ProceduresPharmaceutical PreparationsPhasePolyethylene GlycolsPolymersPopulationPostdoctoral FellowPre-Clinical ModelPrevalenceProcessPropertyProteinsRadiationResearchResearch Project GrantsRiskRisk ReductionSaltsSerumSerum ProteinsStructureSurfaceSystemTechniquesTherapeuticTimeTissuesToxic effectTransfectionTreatment EfficacyTumor TissueWaterWorkbiomaterial compatibilitycancer cellcancer immunotherapycancer therapycancer typechemotherapycrosslinkcytokinedelivery vehicledensitydesignethylene glycolexperienceextracellulargene therapyimmunogenicimmunoreactivityimprovedin vivomacromoleculenanoengineeringnanomaterialsnanoparticlenext generationnucleic acid deliveryparticlepre-clinicalrational designreceptorsmall moleculespatiotemporalsuccesssymposiumtooltrendtumortumor microenvironmentuptake
项目摘要
Project Summary/Abstract
Cancer treatment currently relies on surgery, radiation, and systemic chemotherapy. While these techniques
have greatly improved cancer therapy, they also risk damaging healthy tissue and have incomplete elimination
of the cancer. The use of nanoparticles (NPs) as drug delivery vehicles may reduce these issues by specifically
accumulating in tumor tissue. Further NPs can improve the bioavailability of drugs, widening the range of
potential therapeutics for cancer treatment. Although there have been some successes in the NP field that led
to clinically approved formulations, most have relied on passive means of accumulation and depend on surface
conjugation with polyethylene glycol (PEG) chains. Unfortunately, passive accumulation may not benefit some
cancer types and recent wide-spread use of PEG in commercial products has led to prevalence of anti-PEG
antibodies in the population which risk reducing efficacy of PEG-based therapeutics. Accordingly, there is a great
need to engineer next-generation NPs with improved properties for cancer treatment without the use of PEG.
One promising NP system for cancer drug delivery is layer-by-layer (LbL) NPs which have shown great promise
in preclinical models of cancer as a delivery vehicle for small molecules, nucleic acids or macromolecules. LbL
consists of a simple assembly method involving the alternating adsorption of polymeric species from water onto
a substrate which can be mediated by electrostatics, hydrogen-bonding or other molecular interactions. This
process allows for facile surface modification of NPs which has been shown to enable cancer cell targeting and
to control subcellular localization. However, there is a dearth of knowledge on how to monitor and control the
disassembly of the LbL structure to improve the NP stability and enable precise spatiotemporal control of drug
delivery via LbL-NPs. During the F99 phase, I will explore how to modulate the layer architecture in layer-by-
layer (LbL) NPs. In this project, the effects of solution conditions during layering and other key layer
characteristics will be investigated. Particles will be loaded with interleukin-12, a potent immunostimulatory
protein, to evaluate treatment efficacy of optimized formulations in vitro and in an in vivo metastatic ovarian
cancer model. During the K00 phase, the focus will transition from systemic stability towards characterization of
cellular uptake and intracellular disassembly targeted at gene therapy for cancer treatment. Gene therapy has
had many new exciting breakthroughs in the last decades, but its use in cancer treatment has been limited due
to poor targeting and low transfection efficacy. I will design a library of NP formulations and characterize their
uptake and intracellular disassembly in vitro and in vivo to determine key NP properties that can modulate gene
therapy efficacy. Further, I will design and optimize nucleic acid combinations of new immunotherapeutic
constructs to deliver via the optimized gene therapy formulations.
项目总结/文摘
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Electrostatic adsorption of polyanions onto lipid nanoparticles controls uptake, trafficking, and transfection of RNA and DNA therapies.
聚阴离子在脂质纳米粒子上的静电吸附控制 RNA 和 DNA 疗法的摄取、运输和转染。
- DOI:10.1073/pnas.2307809121
- 发表时间:2024
- 期刊:
- 影响因子:11.1
- 作者:Nabar,Namita;Dacoba,TamaraG;Covarrubias,Gil;Romero-Cruz,Denisse;Hammond,PaulaT
- 通讯作者:Hammond,PaulaT
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Ivan Susin Pires其他文献
Ivan Susin Pires的其他文献
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{{ truncateString('Ivan Susin Pires', 18)}}的其他基金
Engineering Next-Generation Nanoparticles One Layer at a Time
一次一层地设计下一代纳米粒子
- 批准号:
10528938 - 财政年份:2022
- 资助金额:
$ 4.77万 - 项目类别:
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