Development of Chitosan-Carbon Dot Hybrid Nanoemulsomes for MEIS2 Inhibitor Delivery and Bioimaging in Colorectal Cancer

Homeobox protein MEIS2 has been strongly implicated in colorectal cancer (CRC) progression and metastatic potential, making its targeted inhibition a promising therapeutic strategy. However, recently developed MEIS inhibitors are limited by poor aqueous solubility, instability under physiological conditions, and insufficient intracellular accumulation, which restrict their clinical applicability. To overcome these challenges, a multifunctional hybrid nanoemulsome system was developed by integrating boron-silane-doped carbon dots (CDs) with chitosan via glutaraldehyde crosslinking, followed by emulsification with oleic acid and non-ionic surfactants (Span 80 and Tween 20/80) in the presence of a MEIS inhibitor (MEISi-2). The resulting composite exhibited high structural stability, excellent biocompatibility, and a drug encapsulation efficiency of 96.2%. Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) analyses confirmed successful hybridization and the formation of nanoemulsions with an average particle size of approximately 320 nm following drug loading. The system demonstrated controlled drug release under physiological conditions. In vitro studies using HCT116 CRC and HaCaT healthy keratinocytes revealed effective cellular uptake and selective cytotoxicity. The intrinsic fluorescence properties of CDs enabled real-time monitoring of intracellular drug delivery via DAPI-channel imaging. Overall, this hybrid nanoemulsome platform provides a stable and efficient delivery system for MEIS inhibitors and represents a promising strategy for the treatment of CRC. Furthermore, this approach may be extended to other poorly soluble amphiphilic therapeutic agents.