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Endovesiclosis: A Pathway for Translocating Nanoscale Cargo into Extracellular Vesicles

Award Number: K99DE035208
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/06/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Endovesiclosis: A Pathway for Translocating Nanoscale Cargo into Extracellular Vesicles - PROJECT SUMMARY Extracellular vesicles (EVs) are naturally secreted nanoscale particles that mediate intercellular communication by transferring RNA, proteins, and other biomolecules. Their intrinsic biocompatibility and ability to cross biological barriers make EVs attractive candidates for therapeutic delivery. However, clinical translation remains limited by major challenges—including inefficient and nonspecific cargo loading, poor in vivo tracking, and disruption of EV function during conventional engineering methods such as electroporation and sonication. This proposal introduces EVOLVE (Engineering of Vesicles by Optimal Loading Via Endovesiclosis), a force- free, modular strategy for engineering EVs post-isolation with therapeutic cargos such as miRNA and CRISPR– Cas9 RNPs. EVOLVE employs a novel mechanism called endovesiclosis, wherein cationic-arginine– functionalized iron oxide nanoparticles (IONPs) bind cargo electrostatically and enable passive, energy- independent cargo internalization into EVs. Cargo is released intravesicularly through phosphatidylserine- mediated displacement without compromising membrane integrity. This preserves EV bioactivity and avoids the risks associated with genetic modification or physical disruption. Importantly, embedded IONPs enable non- invasive, MRI-based tracking of engineered EVs in vivo—a key step for clinical monitoring. The project will (1) optimize IONP formulations for efficient and safe EV loading across multiple cargo types and (2) evaluate therapeutic efficacy of miR-424– and CRISPR–SMURF1–loaded EVs in a rat calvarial bone defect model. Therapeutic readouts will include µCT, histology, gene modulation, and functional bone regeneration, along with biodistribution and off-target analyses. EVOLVE offers a clinically adaptable EV engineering platform with potential applications across regenerative medicine, gene therapy, and precision nanomedicine. By addressing critical gaps in delivery efficiency, imaging, and biological function, this project supports NIDCR’s mission to advance craniofacial tissue repair and translational nanotherapeutics. It also provides a powerful training framework for the candidate’s transition into an independent research career at the interface of nanotechnology, EV biology, and regenerative medicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $135,522 )
2026	2026	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Oral Diseases and Disorders Research	000	1	8/10/2026	NEW	$135,522
														Subtotal = $135,522

Grand Total All Awards = $135,522

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Endovesiclosis: A Pathway for Translocating Nanoscale Cargo into Extracellular Vesicles

Award Number: K99DE035208

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/06/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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