Chitosan-based fluorescent nanocarriers: A novel drug delivery strategy for oral squamous cell carcinoma therapy

Abstract

Oral squamous cell carcinoma (OSCC) accounts for over 90 % of all oral cancers, underscoring the urgent need for effective treatment strategies to improve patient survival. Grape seed polyphenols (GSP), a naturally occurring plant-derived compound, have shown promise as a therapeutic agent for OSCC. However, their clinical application is limited by poor solubility and instability. To address these challenges, coordination polymers (CPs) were employed as drug carriers, enhancing GSP's solubility, bioavailability, and controlled release. In this study, compound 1 (CP1) was synthesized and incorporated with GSP (CP1@1@GSP), significantly improving drug encapsulation efficiency (over 50 %) and drug loading (16 %), ensuring more effective drug delivery. Despite these advantages, concerns about metal ion release and potential immune responses necessitate further safety evaluation. To mitigate these risks, chitosan (CS), a biocompatible and low-toxicity natural polymer, was introduced. The development of pyrene-modified chitosan-based hollow nanoparticles (Pyrene-CS@CP1@1@GSP) facilitated both drug delivery and fluorescence-based real-time tracking. Characterization using scanning electron microscopy (SEM) and dynamic light scattering (DLS) confirmed the uniform spherical morphology of the nanoparticles, with an average size of approximately 150 nm, stable dispersion, a low polydispersity index (PDI), and excellent self-assembly properties. Further functional evaluation revealed that Pyrene-CS@CP1@1@GSP effectively modulates glycolysis in OSCC cells. Treatment significantly inhibited OSCC cell proliferation in a dose-dependent manner, with glucose levels in the cell supernatant increasing significantly (p < 0.05), indicating reduced glucose uptake by cancer cells. Simultaneously, lactic acid levels decreased (p < 0.05), suggesting suppression of glycolytic activity. Additionally, fluorescence quenching and subsequent restoration of pyrene fluorescence during drug release enabled real-time tracking of drug distribution. These findings demonstrate that Pyrene-CS@CP1@1@GSP enhances the bioavailability and stability of GSP while effectively regulating glycolysis, thereby influencing OSCC progression. This study presents a promising strategy for targeted OSCC therapy, offering both improved treatment efficacy and real-time drug release monitoring, with potential applications in future clinical settings.