1. Academic Validation
  2. Diselenide-Bridged Mesoporous Silica-Based Nanoplatform with a Triple ROS-Scavenging Effect for Intracerebral Hemorrhage Treatment

Diselenide-Bridged Mesoporous Silica-Based Nanoplatform with a Triple ROS-Scavenging Effect for Intracerebral Hemorrhage Treatment

  • ACS Appl Mater Interfaces. 2024 Aug 7;16(31):40739-40752. doi: 10.1021/acsami.4c08726.
Yongju He 1 Meiru Zhang 1 Xiyu Gong 2 3 Xiaoxuan Liu 2 3 Fangfang Zhou 2 3 Binbin Yang 2 3
Affiliations

Affiliations

  • 1 School of Materials Science and Engineering, Central South University, Changsha, Hunan 410083, China.
  • 2 Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha 410083, China.
  • 3 Clinical Medical Research Center for Stroke Prevention and Treatment of Hunan Province, Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha 410083, China.
Abstract

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both Reactive Oxygen Species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN). Edaravone (Eda) was blocked in the pores of DSeMSN by covering the pores with PDA as a gatekeeper. The drug maintained nearly "zero release" before reaching the lesion site, while in the ROS-enriched circumstances, the PDA shell went through degradation and the doped diselenide bonds broke up, triggering the disintegration of nanoparticles and leading to Eda release. Interestingly, the ROS-degradable property of the PDA shell and diselenide bond endowed the system with enhanced ROS-eliminating capacity. The synergistic effect of ROS-responsive drug delivery and ROS-scavenging PDA-DSeMSN showed efficient antioxidative and mitochondria protective performance without apparent toxicity in vitro. Importantly, PDA-DSeMSN@Eda through intravenous administration specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model through antioxidative and antiapoptotic effects with high biological safety. Thus, the PDA-DSeMSN platform holds tremendous potential as an excellent carrier for on-demand delivery of drugs and provides a new and effective strategy for the clinical treatment of ICH.

Keywords

PDA-DSeMSN@Eda; ROS-responsive drug delivery; enhanced ROS-scavenging ability; intracerebral hemorrhage.

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