A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy.

Abstract

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.

• Authors: Jing Yang, Wei Xiong, Lin Huang, Zongheng Li, Qingdeng Fan, Fang Hu, Xiaopin Duan, Junbing Fan, Bo Li, Jie Feng, Yikai Xu, Xiaoyuan Chen, Zheyu Shen
• Journal: Journal of nanobiotechnology (J Nanobiotechnology) Vol. 22 Issue 1 Pg. 204 (Apr 24 2024) ISSN: 1477-3155 [Electronic] England
• PMID: 38658948 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s).

Chemical References

• Sorafenib
• Antineoplastic Agents

Topics

• Ferroptosis (drug effects)
• Animals
• Magnetic Iron Oxide Nanoparticles (chemistry)
• Mice
• Humans
• Drug Delivery Systems (methods)
• Sorafenib (pharmacology, chemistry, therapeutic use)
• Cell Line, Tumor
• Tumor Microenvironment (drug effects)
• Neoplasms (drug therapy)
• Porosity
• Antineoplastic Agents (pharmacology, chemistry, therapeutic use)
• Mice, Inbred BALB C