RT Journal Article SR Electronic T1 Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eabb0616 DO 10.1126/sciadv.abb0616 VO 6 IS 29 A1 Zhao, Zhen A1 Li, Yuanke A1 Liu, Hao A1 Jain, Akshay A1 Patel, Pratikkumar Vinodchandra A1 Cheng, Kun YR 2020 UL http://advances.sciencemag.org/content/6/29/eabb0616.abstract AB IKBKE is an oncogene in triple-negative breast cancer (TNBC), and we demonstrate that IKBKE small interfering RNA (siRNA) inhibits the proliferation, migration, and invasion of TNBC cells. Despite the recent success of siRNA therapeutics targeting to the liver, there still remains a great challenge to deliver siRNAs to solid tumors. Here, we report a hybrid nanocomplex to co-deliver the IKBKE siRNA and cabazitaxel to TNBC to achieve an optimal antitumor effect. The nanocomplex is modified with hyaluronic acid to target CD44 on TNBC cells. The nanocomplex shows higher cellular uptake and better tumor penetration of the encapsulated cargos. The nanocomplex also exhibits high tumor accumulation and antitumor activity in an orthotopic TNBC mouse model. Encapsulation of cabazitaxel in the nanocomplex enhances the activity of the IKBKE siRNA. The hybrid nanocomplex provides a novel and versatile platform for combination therapies using siRNAs and chemotherapy.