Journal of Nanomedicine & Nanotechnology

siRNA delivery with cage-shaped iron oxide nanoparticles to be enhanced by magnetobrownian motion

5^th International Conference on Nanomedicine and Drug Delivery

June 28, 2023 | Webinar

Min A Kang, Justin Fang, Aloka Paragodaarachchi, Keita Kodama, Yuko Ichiyanagi and Hiroshi Matsui

City University of New York, USA
Yokohama National University, Japan
Weill Cornell Medical College, USA

Posters & Accepted Abstracts: J Nanomed Nanotechnol

Abstract:

Superparamagnetic iron oxide nanoparticles (SPIONs) can undergo two types of magnetic relaxations, Néel relaxation or Brownian relaxation, based on the phase difference of the oscillating magnetic moment with respect to the field direction of AMF in alternating magnetic fields (AMFs). First, we investigated whether superparamagnetic cage-shaped iron oxide nanoparticles (IO-nanocages), previously demonstrated to carry payloads inside the cavity for therapeutic molecular delivery, can be controlled to undergo magnetically-induced Brownian motion, dependent on size at the conventional AMF frequency of 335 kHz. The combination of SQUID (superconducting quantum interference device) measurement and computational simulation of the magnetic relaxation time for superparamagnetic IO-nanocages reveals their sizesensitivity to these two relaxation modes. Nanoparticle carriers have been used widely to deliver therapeutic RNAs for gene therapy, overcoming endosomal escape to enhance transfection efficiency remains a major challenge. Here we applied this discovery to trigger endosomal escape by externally-driven Brownian motion of nanoparticles and deliver siRNAs to cytoplasm efficiently. Superconducting quantum interference device (SQUID) measurements reveal the size-sensitivity of Brownian relaxation, and magnetically- driven Brownian motion of IO-nanocages improved siRNA delivery efficiency in cells by reducing luciferase expression to 51% while endosomal membranes were observed to be compromised to release IO-nanocages to cytoplasm in the presence of AMF. This magnetic delivery system was also applied to deliver anticancer therapeutic siRNAs, silencing mGluR5 expression in human and mouse osteosarcoma cell lines, and the proliferation of both human and mouse osteosarcoma cells decreased significantly to 20% with the silencing efficiency via magnetic delivery of IO-nanocages. This outcome suggests that this magnetic delivery method can be further used in future clinical applications in cancer therapy, and we are also exploring the applications of IO-nanocages to intracellular mechano-responsive applications such as mechanotransduction with magnetic fields.