Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

Abstract

Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.

Hybrid Polyelectrolyte Capsules Loaded with Gadolinium-Doped Cerium Oxide Nanoparticles as a Biocompatible MRI Agent for Theranostic Applications

“…These data are consistent with the authors’ earlier data on the antioxidant properties of CeO 2 nanoparticles, which showed that, at the concentration of 10 −5 M, they were able to effectively reduce the generation of radiation-induced hydrogen peroxide [ 30 ]. The redox properties of nanoceria enables it to work as a scavenger of reactive oxygen species (ROS) and free radicals, preventing the development of radiation-induced damage to cells, organs, and whole organisms [ 31 , 32 , 33 , 34 , 35 ]. It has previously been shown that nanoceria is capable of inactivating a wide range of radicals and ROSs, including the hydroxyl radical [ 36 ], nitroxyl radical [ 37 ], singlet oxygen [ 38 ], and superoxide anion radical [ 39 ].…”

Nanozyme-Engineered Hydrogels for Anti-Inflammation and Skin Regeneration

“…Nanotherapeutic approaches have recently demonstrated significant efficacy in addressing RISI [ 244 ]. In a recent approach, microRNA therapy employed in the mesoporous silica (MS)-nCe composites was designed to resolve the radiation-induced ROS [ 245 ]. These nanocomposites could counteract radiation-induced ROS and HIF-1α activation that leads to enhanced healing in radiation-induced wounds.…”

Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application

“…1438 Furthermore, SiO 2 has been reported as a carrier to load nanozymes, natural antioxidants and drugs for relieving inflammation-related radiation-induced skin injury, ischemic stroke and rheumatoid arthritis. 47,1439,1440 Besides, simple loading fulfilling the respective functions of carriers and anti-inflammatory materials, silicon-based materials can also reinforce their own properties through antioxidants. For instance, Zhang et al integrated CeO 2 in BG to co-construct 3D printed scaffolds, in which CeO 2 not only scavenged ROS to eliminate inflammation and promoted mineral deposition for cell proliferation and osteogenic differentiation, but also enhanced the mechanical properties of BG to support new tissue in-growth (Fig.…”