Theranostic silk sericin/SPION nanoparticles for targeted delivery of ROR1 siRNA: Synthesis, characterization, diagnosis and anticancer effect on triple-negative breast cancer

Triple-negative breast cancer (TNBC) has the worst prognosis among all breast cancer subtypes. The lack of proper treatments prompted scientists to find a practical targeted therapy to treat this type of tumor. Based on previous studies, tyrosine kinase-like orphan receptor (ROR1) is overexpressed in TNBC cells. Here, we designed a system consisting of superparamagnetic iron oxide nanoparticles (SPIONs) decorated with silk sericin (SS NPs) for the targeted delivery of ROR1 siRNA, a gene silencer to knockdown the expression of human ROR1 gene. NPs exhibited spherical shape of about 193 nm with acceptable properties both in vitro and in vivo. The apoptosis study showed significant death of MDA-MB-231 cells after 24 h treatment with the prepared NPs. The real-time PCR study also demonstrated an almost complete shutdown of ROR1 expression. Guided by magnetic field, enhanced accumulation of NPs was observed in breast tumors induced by 4T1 cells in BALB/c mice. Histological evaluation of the tumor exhibited necrosis 14 days post-treatment with the siRNA-loaded NPs; whereas, the untreated tumor was proliferating. Also, the tumor growth rate was significantly decreased after treatment with siRNA-loaded NPs in vivo. In conclusion, the prepared delivery system could be considered as a potential ther-apeutic strategy for treating TNBC.

Automated summary

A nanoparticle system for targeted delivery of ROR1 siRNA in the treatment of triple-negative breast cancer was designed and tested. The nanoparticles showed good properties and effectively suppressed tumor cell growth both in vitro and in vivo. The accumulation of nanoparticles in breast tumors was increased by magnetic field guidance. This therapeutic strategy has potential in the treatment of triple-negative breast cancer.