Encapsulation of Plant‐Derived Cycloheptapeptide Mallotumide A in Riboflavin‐Modified Poly(Lactic‐Co‐Glycolic Acid)/Chitosan Nanoparticles

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ABSTRACT Mallotumide A (MA) is a novel cycloheptapeptide isolated from the roots of Mallotus spodocarpus Airy Shaw. It exerts anticancer activity by downregulating several lipogenic enzymes and cellular respiration, particularly in triple‐negative breast cancer. However, MA has poor water solubility and is highly toxic to both cancer and normal cells, limiting its therapeutic applications. To address these drawbacks, MA was encapsulated within poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) and coated with riboflavin (Rf)‐modified chitosan (CR), creating (MA)PLGA/CR NPs. This study characterized the NPs and investigated their encapsulation efficiency of MA, cellular uptake, and anticancer activity in two breast cancer (MDA‐MB‐231 and MCF‐7) and normal (MCF‐10A) cell lines. The NPs were spherical with an average size of 300 ± 6.64 nm and a zeta potential of +11.96 mV. The PLGA/CR NPs exhibited enhanced cellular uptake in both cancer cells in a dose‐ and time‐dependent manner, while reducing toxicity in normal cells. Furthermore, the (MA)PLGA/CR NPs inhibited the viability, migration, and invasion of MDA‐MB‐231 cells, thereby demonstrating their potential as a targeted anticancer delivery system.

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