Cerium Oxide Catalyzed Disproportionation of Hydrogen Peroxide: A Closer Look at the Reaction Intermediate.

Cerium oxide nanoparticles (CNPs) have recently gained increasing interest as redox enzyme-mimetics to scavenge the intracellular excess of reactive oxygen species, including hydrogen peroxide (H2 O2 ). Despite the extensive exploration, there remains a notable discrepancy regarding the interpretation of observed redshift of UV-Visible spectroscopy due to H2 O2 addition and the catalase-mimicking mechanism of CNPs. To address this question, we investigated the reaction mechanism by taking a closer look at the reaction intermediate during the catalase mimicking reaction. In this study, we present evidence demonstrating that in aqueous solutions, H2 O2 adsorption at CNP surface triggers the formation of stable intermediates known as cerium-peroxo (Ce-O2 2- ) and/or cerium-hydroperoxo (Ce-OOH- ) complexes as resolved by Raman scattering and UV-Visible spectroscopy. Polymer coating presents steric hinderance for H2 O2 accessibility to the solid-liquid interface limiting further intermediate formation. We demonstrate in depth that the catalytic reactivity of CNPs in the H2 O2 disproportionation reaction increases with the Ce(III)-fraction and decreases in the presence of polymer coatings. The developed approach using UV-Visible spectroscopy for the characterization of the surface peroxide species can potentially serve as a foundation for determining the catalytic reactivity of CNPs in the disproportionation of H2 O2 .

Synthesis of Stable Cerium Oxide Nanoparticles Coated with Phosphonic Acid-Based Functional Polymers.

Functional polymers, such as poly(ethylene glycol) (PEG), terminated with a single phosphonic acid, hereafter PEGik-Ph are often applied to coat metal oxide surfaces during post-synthesis steps but are not sufficient to stabilize sub-10 nm particles in protein-rich biofluids. The instability is attributed to the weak binding affinity of post-grafted phosphonic acid groups, resulting in a gradual detachment of the polymers from the surface. Here, we assess these polymers as coating agents using an alternative route, namely, the one-step wet-chemical synthesis, where PEGik-Ph is introduced with cerium precursors during the synthesis. Characterization of the coated cerium oxide nanoparticles (CNPs) indicates a core-shell structure, where the cores are 3 nm cerium oxide and the shell consists of functionalized PEG polymers in a brush configuration. Results show that CNPs coated with PEG1k-Ph and PEG2k-Ph are of potential interest for applications as nanomedicines due to their high Ce(III) content and increased colloidal stability in cell culture media. We further demonstrate that the CNPs in the presence of hydrogen peroxide show an additional absorbance band in the UV-vis spectrum, which is attributed to Ce-O22- peroxo-complexes and could be used in the evaluation of their catalytic activity for scavenging reactive oxygen species.

Periodic mesoporous ionosilica nanoparticles for dual cancer therapy: Two-photon excitation siRNA gene silencing in cells and photodynamic therapy in zebrafish embryos.

Photodynamic therapy (PDT) and photochemical internalization (PCI) are two methods that use light to provoke cell death or disturbance of cellular membranes, respectively, via excitation of a photosensitizer and the formation of reactive oxygen species (ROS). In this context, two-photon excitation (TPE) is of high interest for PCI and/or PDT due to spatiotemporal resolution of two-photon light and deeper penetration of near-infrared light in biological tissues. Here, we report that Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) containing porphyrin groups allow the complexation of pro-apoptotic siRNA. These nano-objects were incubated with MDA-MB-231 breast cancer cells, and TPE-PDT led to significant cell death. Finally, MDA-MB-231 breast cancer cells were pre-incubated with the nanoparticles and then injected in the pericardial cavity of zebrafish embryos. After 24 h, the xenografts were irradiated with femtosecond pulsed laser and the size monitoring by imaging showed a decrease 24 h after irradiation. Pro-apoptotic siRNA was complexed with the nanoparticles and incubation with MDA-MB-231 cells did not lead to cancer cell death in dark conditions, but with two-photon irradiation, TPE-PCI was observed and a synergic effect between pro-apoptotic siRNA and TPE-PDT was noticed, leading to 90% of cancer cell death. Therefore, PMINPs represent an interesting system for nanomedicine applications.

Periodic Mesoporous Ionosilica Nanoparticles for BODIPY Delivery and Photochemical Internalization of siRNA.

Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) made via co-condensation reactions starting from an ionosilica precursor and a porphyrin derivative were used for simultaneous BODIPY/siRNA delivery in cancer cells. We observed high BODIPY loading capacities and efficiencies of the PMINPs that are triggered by anion exchange. siRNA adsorption took place on the surface of the nanoparticles, whereas BODIPY was encapsulated within the core of the nanoparticles. BODIPY release was found to be pH-dependent. Our results indicate 94 % BODIPY release after 16 h at pH 4, whereas only 2 % were released at pH 7.4. Furthermore, complexation with siRNA against luciferase gene was observed at the surface of PMINPs and gene silencing through its delivery via photochemical internalization (PCI) mechanism was efficient in MDA-MB-231 breast cancer cells expressing stable luciferase.

Periodic Mesoporous Ionosilica Nanoparticles for Green Light Photodynamic Therapy and Photochemical Internalization of siRNA.

We report periodic mesoporous ionosilica nanoparticles (PMINPs) as versatile nano-objects for imaging, photodynamic therapy (PDT), and efficient adsorption and delivery of small interfering RNA (siRNA) into breast cancer cells. In order to endow these nanoparticles with PDT and siRNA photochemical internalization (PCI) properties, a porphyrin derivative was integrated into the ionosilica framework. For this purpose, we synthesized PMINPs via hydrolysis-cocondensation procedures from oligosilylated ammonium and porphyrin precursors. The formation of these nano-objects was proved by transmission electron microscopy. The formed nanoparticles were then thoroughly characterized via solid-state NMR, nitrogen sorption, dynamic light scattering, and UV-vis and fluorescence spectroscopies. Our results indicate the formation of highly porous nanorods with a length of 108 ± 9 nm and a width of 54 ± 4 nm. A significant PDT effect of type I mechanism (95 ± 2.8% of cell death) was observed upon green light irradiation in nanoparticle-treated breast cancer cells, while the blue light irradiation caused a significant phototoxic effect in non-treated cells. Furthermore, PMINPs formed stable complexes with siRNA (up to 24 h), which were efficiently internalized into the cells after 4 h of incubation mostly with the energy-dependent endocytosis process. The PCI effect was obvious with green light irradiation and successfully led to 83 ± 1.1% silencing of the luciferase gene in luciferase-expressing breast cancer cells, while no gene silencing effect was observed with blue light irradiation. The present work highlights the high potential of porphyrin-doped PMINPs as multifunctional nanocarriers for nucleic acids, such as siRNA, with a triple ability to perform imaging, PDT, and PCI.