A novel bioengineered spider silk-based particle for the delivery system of chemotherapy drugs

Spider silk protein (spidroin) is the primary constituent of spider silk fibers and exhibits remarkable biocompatibility, thermal stability, and biodegradability, making it a promising biomaterial for biomedical applications, particularly in drug delivery. Currently, drug delivery systems utilizing spidroins predominantly focus on engineered dragline spidroins. However, research on other spidroin types—such as aciniform spidroins (AcSp) —in their application as biomaterials within drug delivery systems remains very limited. Here, we engineered the recombinant spidroin AS2, derived from the Araneus ventricosus AcSp2 protein repeat domain, and designed a modified version, eAS2, by incorporating an additional glutamic acid residue. Both AS2 and eAS2 proteins exhibited self-assembly properties, forming non-toxic nanoparticles with similar secondary structure content in potassium phosphate buffer but differed in zeta potential values. Although eAS2 particles demonstrated high loading efficiency for positively charged drugs like mitoxantrone (MTX), a rapid release rate was also noted for MTX-loaded eAS2 particles. Conversely, the combination of efficient loading and a desirable slow release profile renders eAS2 particles an optimal delivery system for neutral and positive charged drugs, such as etoposide (ETP) and doxorubicin (DOX).