Engineering magnetosomes with chimeric membrane and hyaluronidase for efficient delivery of HIF-1 siRNA into deep hypoxic tumors

Abstract

Hypoxia-inducible factor-1 (HIF-1) plays a critical role in tumor development and chemotherapy resistance, and suppression of HIF-1 has emerged as a captivating antitumor approach. To efficiently silence HIF-1 in deep hypoxic tumors, we herein developed a versatile small interfering RNA delivery system that could overcome multiple physiological barriers. The system is comprised of an Fe3O4 magnetic nanocluster as the core, pre-engineered chimeric membrane for the cloak, and decorated hyaluronidase on the surface, which succeeded in prolonged circulation time, magnetic resonance imaging guidance, magnetic tumor accumulation, hypoxic site penetration, homotypic tumor targeting, and cytoplasmic trafficking. Such versatile and programmed delivery performance enabled the engineered magnetosomes to achieve the remarkable silencing of HIF-1, potent therapeutic effect and chemoresistance amelioration with few abnormalities, showing a promising modality for anticancer therapy.