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.