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Principal Investigator: Emily S Day
Organization: UNIVERSITY OF DELAWARE
Fiscal Year: 2024
Award: $408,005
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY/ABSTRACT
The Day Lab engineers nanoparticles (NPs) with unique physicochemical properties to transform the
treatment of various diseases and elucidates how architecture impacts function by studying nano/bio interactions
from the subcellular to whole organism level. The NPs we develop enable high precision therapy by: (1) delivering
antagonistic antibodies or nucleic acids to cells to inhibit genes that drive disease progression, (2) supplying heat
or other payloads only to diseased cells in response to activation with tissue-penetrating near-infrared light, or
(3) facilitating cell-specific cargo delivery by using cell-derived membranes as coatings that minimize immune
recognition and enable target cell binding. We are applying our technologies to manage aggressive cancers,
blood disorders, and maternal/fetal health conditions. Further, we are proving through rigorous studies that both
what is packaged in NPs and how it is packaged dictate therapeutic potency. Much of our work advancing
nanomedicine over the last five years was funded by the MIRA program. Moving forward, we will use our acquired
tools and knowledge to probe unanswered questions in nanomedicine and advance the ability of NPs to surpass
biological barriers.
There is currently an undesired disparity between preclinical and clinical performance of nanomedicines
that is driven by biological barriers that limit NP delivery efficiency, efficacy, and safety. These include immune
barriers (protein corona formation leading to macrophage clearance), vascular barriers (limited extravasation),
and tissue barriers (poor penetration through extracellular matrix, mucus, etc. to reach desired cells in
heterogeneous populations). Over the next five years we will address these biological barriers through
mechanistic studies that incorporate and adapt NPs previously developed in our lab to enhance delivery and
efficacy. Specifically, we will investigate questions related to protein corona-mediated immune clearance, the
role of inflammation in NP extravasation, and NP interaction with reproductive tissue barriers and the vaginal
microbiome. Answering these questions will guide the development of NPs with improved clinical performance.
In addition to advancing the broader field of nanomedicine, the information gained will lead into the long-term
research of the Day Lab addressing both extracellular and intracellular barriers to nanomedicine. Overall, our
work has both basic scientific and translational significance, and our discoveries will transform the application of
nanomedicine to diverse healthcare problems by developing technologies with unmatched clinical performance.
Terms: <Address><Antibodies><Architecture><Artificial nano particles><Artificial nanoparticles><Binding><Biological><Blood Diseases><Blood Vessels><Body Tissues><COVID-19><CV-19><Cancers><Cell Body><Cell-Extracellular Matrix><Cells><Clinical><Coronavirus Infectious Disease 2019><Development><Disease><Disease Management><Disease Progression><Disorder><Disorder Management><Disparities><Disparity><ECM><Engineering / Architecture><Extracellular Matrix><Extravasation><Fetal health><Funding><Genes><Goals><Healthcare><Hematologic Diseases><Hematological Disease><Hematological Disorder><Immune><Immunes><Inflammation><Knowledge><Lead><Leakage><Light><Macrophage><Malignant Neoplasms><Malignant Tumor><Mediating><Membrane><Molecular Interaction><Mucous body substance><Mucus><Mφ><Nucleic Acids><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Pb element><Penetration><Performance><Photoradiation><Population Heterogeneity><Precision therapeutics><Property><Proteins><QOL><Quality of life><Research><Role><Safety><Spillage><Technology><Therapeutic><Tissues><Treatment Efficacy><Whole Organism><Work><biologic><biological systems><blood disorder><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><developmental><diverse populations><engineered nano particle><engineered nanoparticle><extracellular><health care><heavy metal Pb><heavy metal lead><heterogeneous population><immune clearance><immune elimination><improved><intervention efficacy><malignancy><membrane structure><mucous><nano><nano medicinal><nano medicine><nano particle><nano particle delivery><nano-sized particle><nanomedicinal><nanomedicine><nanoparticle><nanoparticle delivered><nanoparticle delivery><nanoparticle therapy><nanosized particle><neoplasm/cancer><new approaches><novel approaches><novel strategies><novel strategy><patient oriented outcomes><population diversity><pre-clinical><precision therapies><precision treatment><preclinical><programs><reproductive><response><social role><therapeutic efficacy><therapeutic nanoparticles><therapy efficacy><tool><vaginal biome><vaginal microbiome><vascular>