# Supplement:  Developing Nanoparticle Drug Delivery Systems for Venous Malformations

> **NIH NIH K08** · BOSTON CHILDREN'S HOSPITAL · 2024 · $75,600

## Abstract

Project Summary
The objective of this proposal is to develop targeted therapies for venous malformations (VMs). VMs
are slow-flow vascular lesions associated with disfigurement, pain, and functional impairment.
Recently, systemic inhibition of the mammalian target of rapamycin (mTOR) with sirolimus has proven
efficacious for treating children with complex VMs. However, systemic drug delivery is associated with
side effects that limit treatment. Therefore, safe, targeted therapies that minimize systemic toxicity are
required.
The proposed project will develop nanoparticulate (NP) targeted drug delivery systems to achieve
high local drug concentration in VMs while minimizing systemic distribution. This will be achieved by
virtue of enhanced permeation and retention (EPR), a well-recognized phenomenon in cancer biology
whereby leaky tumor vasculature allows for preferential uptake of nanoparticles compared to uptake
in tissues with normal vasculature. Passive NP accumulation within VMs, due to EPR, will be
enhanced with active targeting techniques, such as photo-targeting. The surfaces of NPs will be
coated with molecules that encourage cell uptake. These molecules will be inactivated with a “caging
group,” a reversibly bound molecule that is sensitive to a specific wavelength of light. Upon irradiation
with light, the caging molecule will be removed from the NP. Therefore, NPs can be systemically
injected and remain unbound to tissues. However, irradiation of the VM will cause “uncaging” to occur,
which will activate the NPs, and allow for enhanced NP binding and drug release at the target site.
To test this hypothesis, we propose three specific aims: Specific Aim 1: Formulation and
characterization of NPs with prolonged dwell times in VMs. Specific Aim 2: Study of targeted NP drug
delivery systems in vivo. Specific Aim 3: Study of NP drug delivery systems on therapeutic efficacy in
vivo. With the guidance and mentorship of Dr. Daniel Kohane, Dr. Cullion has developed a career
development plan to provide the mentored research, technical skill development, and didactic training
needed to achieve her goals of (1) becoming an expert in nanomedicine and drug delivery for the
treatment of VMs and (2) achieving scientific independence and becoming an R01 funded physician-
scientist with a career in translational research focused on nanomedicine and drug delivery for
vascular anomalies.

## Key facts

- **NIH application ID:** 11111578
- **Project number:** 3K08HL153782-03S1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Kathleen Cullion
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $75,600
- **Award type:** 3
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11111578

## Citation

> US National Institutes of Health, RePORTER application 11111578, Supplement:  Developing Nanoparticle Drug Delivery Systems for Venous Malformations (3K08HL153782-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/11111578. Licensed CC0.

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