Targeted Photodynamic Therapy for Endometrial Cancer Using Folic Acid Conjugated Graphene Quantum Dots-Hexagonal Boron Nitride Nanoassemblies

Abstract

Endometrial cancer is the most common gynecological cancer in the United States, with current treatment options frequently being limited by a lack of specificity, increased toxicity, and moderate therapeutic efficacy. Photodynamic therapy (PDT) is a minimally invasive alternative to standard of care. PDT in the management of endometrial cancer has challenges such as oxygen dependency, poor light penetration, and biodistribution of photosensitizing agents. In this study, we developed a novel folic acid conjugated graphene quantum dot-hexagonal boron nitride (FA-GQBN) nanoassembly intended for targeted endometrial cancer PDT. GQDs were synthesized using a green, bottom-up approach using rice powder and incorporated onto hBN nanosheets to further provide stability. The nanocomposites were PEGylated to limit the aggregation and functionalized with folic acid (FA) to allow for receptor-mediated targeting of folate-receptor-positive endometrial cancer cells. Confirmation of successful synthesis, conjugation, and cellular uptake was performed using FTIR, DLS, TEM, and CLSM techniques. In vitro cytotoxicity studies using XTT and LDH assays confirmed the biocompatibility of FA-PEG-GQBN nanocomposites and showed inconclusive results for testing ROS. In vivo studies established a subcutaneous HEC1A model of an endometrial tumor. There was no detectable fluorescence of our nanoassemblies, and FA did not enhance tumor localization. Despite this, FA-GQBN nanocomposites remain a promising platform for targeted photodynamic therapy in endometrial cancer.