Nanoengineered Chitosan–Genipin Coating of Yeast-Derived Biopolymer Microcapsules for Theranostic Applications

The development of effective and trackable drug delivery systems remains a major challenge in anticancer therapy. In this study, we designed novel polysaccharide-based theranostic carriers using a yeast-shell (YC) framework, providing a biocompatible platform for intracellular drug delivery. For the first time, a chitosan–genipin bioconjugate was synthesized via a solvent-free, green mechanochemical method and applied as an outer coating to microcarriers encapsulating the anticancer drug 5-fluorouracil (5-FU) and the fluorescent dye phenosafranin. The resulting system enabled simultaneous fluorescence tracking and the controlled release of the chemotherapeutic agent. In vitro evaluation using the MDA-MB-231 triple-negative breast cancer cell line demonstrated that 5-FU retained its antiproliferative activity, while the carriers facilitate sustained intracellular delivery. These findings highlight the potential of YC-based polysaccharide carriers, surface- modified with chitosan–genipin to enhance hydrophilicity, as a versatile platform for anticancer therapy, combining biocompatibility, traceability, and controlled drug release.