Icon Legend

This session is not in your schedule.

This session is in your schedule. Click again to remove it.

Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session E

S21 - Development of Targeted Multifunctional Nanoparticles for In Vitro and In Vivo Peripheral Artery Disease Theragnostic

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

BK

Brooke Kerk

Undergraduate Research Assistant
University of Texas at Arlington, United States

Co-Author(s)

Na Nguyen

Doctoral Student
The University of Texas at Arlington
FORT WORTH, Texas, United States
EG

Ethan M. Gerhard

Post Doctoral Scholar
Pennsylvania State University
University Park, Pennsylvania, United States
BA

Bushra Afzal

Postdoctoral Fellow
University of Texas Southwestern Medical Center, United States
KL

Khiem Le

Graduate Research Assistant
University of Texas at Arlington, United States
VT

Vy Tran

Graduate Research Assistant
University of Texas at Arlington
Fort Worth, Texas, United States
Su Yan

Professor
Pennsylvania State University, United States
Li Liu

Associate Professor
University of Texas Southwestern Medical Center
Dallas, Texas, United States

Primary Investigator(s)

Kytai T. Nguyen

Professor
The University of Texas at Arlington
Arlington, Texas, United States

Co-Author(s)

TN

Tam Nguyen

Assistant Professor of Research
The University of Texas at Arlington
Arlington, Texas, United States

Introduction: : Peripheral artery disease (PAD) affects 8–10 million people in the U.S., mostly over age 65, and results from plaque buildup in lower limb arteries, leading to reduced blood flow, muscle ischemia, and, in severe cases, limb loss or death. Current treatments are often invasive and risky, emphasizing the need for safer alternatives. Nanoparticles (NPs) offer a promising solution for non-invasive, targeted, and sustained drug delivery. However, tracking these NPs in vivo experiments remains a challenge due to toxicity of dyes. To address this, we developed targeted multifunctional nanoparticles (T-MNPs) to a drug delivery platform for PAD treatment management. By using intrinsic fluorescent and photoacoustic properties of biodegradable photoluminescent polymer adenine tetramer copper oxide (BPLPAT CuO) prepolymer, these nanocarriers allow to track ECs in vitro studies and detect their localization in ischemic tissues on PADs. cLABL targeting peptides were used to target ICAM-1 upregulated in ischemic tissues on PADs. This dual-function platform holds strong potential for PAD treatment, enhancing both safety and efficacy through integrated therapy and diagnostic tracking.

Materials and

Methods: : Multifunctional nanoparticles (MNPs) were synthesized using BPLPAT CuO pre-polymer. cLABL targeting peptides were conjugated to MNPs surface (T-MNPs) via carbodiimide chemistry. Particle sizes and surface charges were characterized using a ZetaView instrument. In vitro imaging performance was assessed by evaluating MNPs uptake in human endothelial progenitor cells (EPCs) under fluorescent microscopy. Multispectral optoacoustic tomography (MSOT) was used to detect photoacoustic signals of MNPs. Hemocompatibility was tested using a hemolysis assay, and cytocompatibility was evaluated with an MTS assay across a range of NPs concentrations. T-MNPs were tested on mouse PAD model to evaluate imaging properties and targeting efficacies.

Results, Conclusions, and Discussions:: T-MNPs were fabricated with an average diameter of approximately 150 nm. T-MNPs exhibited good cytocompatibility and acceptable hemocompatibility, with hemolysis remaining below 5% at concentrations up to 1000 µg/ml. Fluorescence microscopy confirmed strong NPs uptake by endothelial progenitor cells (EPCs), with Cy5 signals observed in the cytosol without the need for external dyes, while nuclei appeared blue. In vivo, multispectral optoacoustic tomography (MSOT) imaging demonstrated photoacoustic signals from the NPs were clearly detected at 800 nm in both color and grayscale MSOT images. Microscopically, T-MNPs exhibited significantly higher accumulation—at least threefold—in the gastrocnemius muscle of PAD mice compared to the control group, as observed via the Cy5 channel using fluorescence microscopy one week after intravenous injection.
Our findings show that BPLP-based multifunctional nanoparticles are safe, effective for PAD treatment, and enable real-time, non-invasive tracking of targeted accumulation in ischemic tissues. Future studies will focus on evaluating toxicity effects, biodegradation, and targeting specificity in vitro and in murine PAD models. These will include histological and functional analyses to assess sustained angiogenesis and limb recovery. This integrated theragnostic platform has strong potential as a safe, image-guided, and minimally invasive approach for PAD management, with broader applications in ischemic vascular diseases.

Acknowledgements and/or References (Optional): : This research was supported by NIH R15 HL156076, NIH R01 HL158204, and AHA 25AIREA1357216.