Rod-shaped nanoparticles have been reported to exhibit improved cellular uptake, intracellular processing and transport through tissues and organs, as compared to spherical nanoparticles. We use C-S-B triblock polypeptides composed of a collagen-like block (C), a silk-like block (S) and an oligolysine domain (B) for one-dimensional co-assembly with siRNA into rod-shaped nanoparticles. Here we investigate these siRNA encapsulating rod-shaped nanoparticles as a gene delivery system. Uptake experiments for C-S-B and C-S-B/siPlk1 particles indicate that these rod-shaped nanoparticles can efficiently deliver siPlk1 into HeLa cells. Moreover, C-S-B/siPlk1 complexes display significant mPlk1 gene knockdown in a dose-dependent manner, causing apoptosis as intended. The lower effectiveness of C-S-B/siPlk1 in inducing cell death as compared to cationic lipid-based formulations is explained by the high lysosome-C-S-B/siPlk1 co-localization ratio, which will need to be addressed in a future redesign of polypeptide sequence. Overall, the non-toxic and unique rod-shaped C-S-B nanoparticles deserve further optimization as a new siRNA delivery system for cancer therapy.
Keywords: Nanoparticles; Polypeptide; siRNA delivery.
Copyright © 2020. Published by Elsevier B.V.