Poster S8 - Protein Chaperoned Semiconducting Polymer Nanoparticles with Improved NIR-I Photophysical Properties and Dual-Receptor Targeting of Solid Tumors

Introduction: Ovarian cancer is characterized by extremely aggressive gynecological tumors that exhibit low survival rates. Most of the patients are diagnosed at an advanced stage, where extensive metastasis of tumor cells to the abdominal cavity has begun. At present, surgery is the primary curative option using visual inspection and palpations with the goal of removing as much of the tumors as possible to avoid recurrence or metastases, however, such an approach is risky and reduces the quality of life of patients. Fluorescence-based image-guided surgery (FIGS) has risen to prominence by providing surgeons with real-time feedback on tumors in an intraoperative setting by providing a high-contrast imaging difference between tumor tissues and normal tissues. FIGS methods have a lack of non-ionizing radiations compared to other clinical modalities like MRI or CT. FIGS uses imaging agents in the near-infrared range (700-900nm) due to lower tissue autofluorescence, reduced scattering, and comparatively higher tissue penetration in this region. The current repertoire of imaging agents has limitations in low fluorescence quantum yields, non-specific protein adsorption, rapid clearance from blood, and falls short in achieving complete removal of ovarian cancer lesions. To address these inadequacies, a universal probe is needed with the ability to provide high contrast between tumors and background tissues across all stages of ovarian cancer – from primary tumors to metastatic ones.

Materials and

Methods: Firstly, employing a combination of molecular docking and experimental studies, we demonstrate that an albumin coating significantly improves the long-term colloidal stability, brightness, and fluorescence quantum yield of BSA@SPs compared to conventional polymer-lipid coatings. Secondly, we modify albumin to incorporate folate receptor targeting for primary ovarian cancer and leverage albumin's inherent ability to target secreted protein acidic rich in cysteine (SPARC) receptors that are overexpressed on metastatic tumors. Nanoparticle synthesis is done using a probe sonicator and a hot plate stirrer, both manufractured by Fischer Scientific, for conjugation. To isolate a nanoparticle solution with the desired size and polydispersity index value, a Thermo Scientific ST Plus Series centrifuge is used to simultaneously filter the solution. To conduct physiochemical characterization of synthesized nanoparticles, dynamic light scattering and zeta potential data was collected using the Litesizer DLS 700 by Anton Parr. An In Vivo Imaging System (IVIS) was used to obtain tissue penetration abilities of different nanoparticles.

Results, Conclusions, and Discussions: Our BSA optimization studies showed that nanoparticles with 100µm BSA had improved colloidal and size stability. BSA coated with PCPDTBT dye exhibited greater NIR-I fluorescence brightness and quantum yield values than the polymer-lipid counterparts (DSPE-PEG). ​BSA@SP2 tumor-mimicking phantoms also display significantly higher signal-to-background discrimination in increasing tissue depths, thereby better suited for image-guided cancer surgeries. When increasing the targeting abilities of our nanoparticle solutions, by increasing the concentration of the folate receptor, the imaging capabilities remained unchanged. ​We will evaluate out BSA@SP2 solutions in in vitro ovarian cancer models of early stage and metastatic stages (IBC-2023-1085), followed by evaluation in vivo mice models of metastatic ovarian cancer. ​Employing alternative polymer conjugates and dyes into our nanoparticle design may improve molecular docking ang NIR fluorescence for future studies. We anticipate that BSA@SPs nanoparticles can serve multiple purposes, including pre-operative evaluation by assessing the location and size of ovarian cancer, intraoperative navigation to guide surgery effectively, and post-surgery monitoring for tumor recurrence. By enhancing surgery efficiency and reducing tumor recurrence, our nanoparticle-based imaging agents hold promise for significant advancements in ovarian cancer management.​

Acknowledgements (Optional): I would like to thank the Honors College Undergraduate Research Scholars Program supported by The CH Foundation and the Helen Jones Foundation, Inc. I would like to acknowledge the Department of Mechanical Engineering for providing laboratory funding to the Srivastava Lab. I would also like to thank the Experimental Sciences Building II faculty for allowing us to analyze samples with the IVIS. ​