Poster S15 - Aromatic Interactions-Driven Polymer-Lipid Nanoparticles for Pre, Intra, and Post-Operative Image-Guided Interventions of Tumor Metastases

Introduction: In the quest to combat cancer, researchers are constantly seeking innovative ways to enhance surgical precision and reduce the risk of recurrence. Traditional methods often involve the removal of excess healthy tissue, leading to high positive margin rates, especially with non-palpable cancers. To address this challenge, fluorescence image-guided surgery has emerged as a promising technique, leveraging optically active dyes like indocyanine green (ICG) or pafolacianine (OTL-38) to visualize tumors. However, these dyes have limitations, dissipating quickly in the body and providing only partial visibility of tumor margins. Addressing this issue, we have developed a polymer-lipid nanoparticle encapsulating a near-infrared emitting semiconducting polymer (PCPDTBT) and a CT-responsive molecule (2,3,5-triiodobenzoic acid, TIBA). By gradually increasing interactions between these molecules, the nanoparticles achieve both NIR-I fluorescence emission and computed tomography (CT) imaging capabilities. These nanoparticles offer simultaneous NIR-I fluorescence and CT signals allowing dual-modal imaging of lung metastatic tumors both in vivo and in vitro, enabling preoperative CT evaluation, intraoperative NIR-fluorescence navigation, and post-surgery monitoring for tumor recurrence.

Materials and

Methods: A molecular docking study was conducted by the UCF Chimera software to analyze the interactions between PCPDTBT and 2,3,5-Triiodobenzoic Acid (TIBA). To analyze the CT responsiveness, we synthesized three nanoparticles, one with no CT agent at all and two with CT agent at different concentrations. The solution was made using DSPE-PEG and DSPE-PEG-crgd to coat the particle and the dyes, PCPDTBT, and TIBA were used to be trapped in the core of the particles. All of them were soluble in THF(Tetrahydrofuran). Following the synthesis protocol, we used the nanoprecipitation method in DI water to get the particles. After the synthesis, the particles were filtered through the 0.22-micron filter to get rid of any unbound particles. All the characterization was done using a DLS lite sizer, Fluorescence spectrometer, and UV-VIS absorbance in The Srivastava Lab at Texas Tech University. The IVIS images were collected using the IVIS imager in the Texas Tech University Experimental Science Building facility.

Results, Conclusions, and Discussions: The molecular docking study validates our design strategy for the nanoparticle. Both the PCPDTBT dye and TIBA are hydrophobic, and they share a strong hydrophobic-hydrophobic bond and because of their aromatic rings, they have strong π-π bonds. This molecular interaction allows the nanoparticle to deliver more amount of optical agents to the targeted tumor cells. Thus, the polymer-lipid nanoparticles with dual-modal fluorescence and CT signals have been prepared to leverage molecular interaction. The physicochemical characterization shows that the nanoparticles have excellent long-term colloidal stability and optical stability. The IVIS imaging shows promising results for using both PCPDTBT and TIBA together as the NPs with CT agent give brighter fluorescence. The next step involves demonstrating the efficacy of these nanoparticles in tumor-mimicking phantoms and advancing to in vivo mouse model investigations. If successful, this technology could revolutionize cancer surgery, providing surgeons with unprecedented precision and improving patient outcomes.

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