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Development of Chitosan-Carbon Dot Hybrid Nanoemulsomes for MEIS2 Inhibitor Delivery and Bioimaging in Colorectal
Buğra Onat1, Deniz Özol1, Seda Karakaş1
1Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, 34775 Istanbul, Türkiye.
Abstract:
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.
Insights
A novel nanoemulsome system enhances MEIS inhibitor delivery for colorectal cancer (CRC) treatment. This stable, biocompatible platform improves drug solubility and cellular uptake, offering a promising therapeutic strategy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Homeobox protein MEIS2 is crucial in colorectal cancer (CRC) progression and metastasis.
- Existing MEIS inhibitors face challenges like poor solubility and instability, limiting clinical use.
Purpose of the Study:
- To develop a stable, efficient drug delivery system for MEIS inhibitors.
- To overcome limitations of current MEIS inhibitors for improved CRC treatment.
Main Methods:
- Created a hybrid nanoemulsome by integrating boron-silane-doped carbon dots (CDs) with chitosan and a MEIS inhibitor (MEISi-2).
- Characterized the system using FTIR and DLS, assessing drug encapsulation efficiency, stability, and particle size (~320 nm).
- Evaluated in vitro drug release, cellular uptake, and cytotoxicity in HCT116 CRC and HaCaT cells.
Main Results:
- Achieved 96.2% drug encapsulation efficiency with high structural stability and biocompatibility.
- Demonstrated controlled drug release under physiological conditions.
- Showcased effective cellular uptake and selective cytotoxicity in cancer cells, with CD fluorescence enabling real-time delivery monitoring.
Conclusions:
- The hybrid nanoemulsome platform offers a stable and effective delivery system for MEIS inhibitors.
- This approach shows potential for advancing CRC treatment and can be applied to other poorly soluble drugs.
