Multimodal Imaging of Protein-Based Biomaterials for Delivering Chemo-Agent Cargo for Glioblastoma Treatment in a Murine Model

Author

Orin Mishkit, CUNY City CollegeFollow

Date of Award

2025

Document Type

Thesis

Department

Biology

First Advisor

Youssef Z. Wadghiri

Second Advisor

Karen Hubbard

Keywords

Glioblastoma Multiforme, Nanomicelle Drug Delivery, Biomaterial-based Slow Release, Bioluminescence Imaging, Magnetic Resonance Imaging, Theranostics

Abstract

Protein-based self-assembling biomaterials, known as Thermo-Responsive Assembled Proteins (TRAP), present meaningful potential as drug delivery carriers. These materials enable the controlled, slow release of poorly soluble chemotherapeutic agents, such as doxorubicin (Dox), while potentially reducing systemic off-target effects. In collaboration with multiple NYU labs, this study evaluated the efficacy of two TRAP variants—TRAP and F-TRAP—as drug delivery carriers in a xenograft mouse model of glioblastoma multiforme (GBM).

The primary objective was to compare the effectiveness of TRAP-loaded Dox (TRAP-DOX) to free Dox in achieving tumor extravasation and accumulation, facilitating sustained drug release. We hypothesized that the leaky vasculature of GBM tumors would promote TRAP-DOX localization and prolonged Dox delivery via the enhanced permeation and retention (EPR) effect, thereby improving therapeutic efficacy while minimizing side effects.

Therapeutic efficacy was assessed by administering equivalent doses of Dox across treatment groups, with bimodal in vivo imaging employed for evaluation. Bioluminescence imaging (BLI) tracked tumor cell activity and progression, while magnetic resonance imaging (MRI) measured end-stage tumor volume.

Preliminary results indicated that F-TRAP-DOX exhibited comparable therapeutic performance to free Dox, with a slight, non-significant trend toward reduced tumor burden observed via BLI and MRI. In contrast, TRAP-DOX was less effective than free Dox, likely due to the 55% increase in drug-loading capacity of F-TRAP over TRAP, which may improve therapeutic delivery and release profiles.

As a secondary objective, we aimed to enhance the accuracy and reproducibility of BLI through a comprehensive imaging strategy. Analysis of bioluminescence (BL) kinetic curves revealed a significant shift in the kinetic profiles after four weeks of GBM xenograft growth, with the time to peak emission increasing from 20 to 32 minutes on average. Additionally, peak BL signal demonstrated a stronger correlation with end-stage tumor volume compared to signals acquired using a fixed delay (R² = 0.812 vs. R² = 0.640).

These findings suggest that while F-TRAP-DOX may offer slight therapeutic advantages over free Dox, further optimization of TRAP-based drug delivery systems is warranted to fully realize their potential for GBM treatment. Additionally, this study highlights the need for a deeper understanding of tumor staging and its impact on animal physiology, particularly as it relates to luciferin uptake and BL signal kinetics. Changes in tumor microenvironment and vascular properties over time may significantly influence drug delivery and imaging outcomes, emphasizing the importance of accounting for these variables in future studies.

Recommended Citation

Mishkit, Orin, "Multimodal Imaging of Protein-Based Biomaterials for Delivering Chemo-Agent Cargo for Glioblastoma Treatment in a Murine Model" (2025). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/1232