Shell Silica Nanoparticles Research Articles

Self-healing glassy hybrids based on imidazole-functionalized silica nanoparticles with zinc complexes using dynamic and reversible cross-linking

Self-healing glass materials can potentially overcome the inherent limitations of glass, such as brittleness and difficulties in repairing broken sections while maintaining its critical properties. This paper reports a structural design and synthetic strategy for preparing glassy self-healing hybrids with high silica contents. The developed hybrids exhibited excellent self-healing properties based on dynamic and reversible crosslinking owing to the high density of zinc/imidazole units on the silica surface. First, core–shell silica nanoparticles with small multifunctional imidazole/butyl units (diameter: approximately10 nm) and good processability (homogeneous colloidal dispersions in common organic solvents) were synthesized. Afterwards, imidazole-functionalized silica nanoparticles were fabricated using Zn species to obtain self-healing hybrids with high silica contents (>60 wt%). These nanoparticles served as multifunctional and reversible crosslinking sites that dissipated energy, resulting in excellent mechanical, thermal, and healing characteristics. The obtained zinc/imidazole-based silica hybrids remain solid with high storage elasticity in the temperature range of 25–160 °C and high thermal stability corresponding to a 5 wt% weight loss above 280 °C, which were critical for self-healing glass applications. They also exhibited a moderate Young’s modulus of 330 MPa and a self-healing recovery efficiency of 87%. The findings of this study provide new insights into the roles of reversible interactions (metal/ligand exchange reactions) at particle–particle interfaces and high surface functionalities that serve as non-covalent crosslinking points. The prepared hybrids with high silica contents remain solid over a wide temperature range, which can open new avenues for self-healing glass materials.

Multimodal Spectroscopy Assays for Advanced Nano-Optics Approaches by Tuning Nano-Tool Surface Chemistry and Metal-Enhanced Fluorescence

In this research work, different chemical modifications were applied to gold nanoparticles and their use in enhanced non-classical light emitters based on metal-enhanced fluorescence (MEF) was evaluated. In order to achieve this, gold core–shell nanoparticles with silica shells were modified via multilayered addition and the incorporation of a covalently linked laser dye to develop MEF. Their inter-nanoparticle interactions were evaluated by using additional silica shell multilayers and modified cyclodextrin macrocycles. In this manner, the sizes and chemical surface interactions on the multilayered nanoarchitectures were varied. These optical active nanoplatforms led to the development of different nanoassembly sizes and luminescence behaviors. Therefore, the interactions and nanoassembly properties were evaluated by using various spectroscopic and nanoimaging techniques. Highly dispersible gold core–shell nanoparticles with diameters of 50–60 nm showed improved colloidal dispersion that led to single ultraluminescent gold core–shell nanoparticles with MEF. Then, the addition of variable silica lengths produced increased interactions and consequent nanoaggregation. However, the silanized nanoparticles were easily dispersible after agitation or sonication. Thus, their sizes were proportional only to the diameter and the van de Waals interaction did not affect their sizes in bulk. Then, the covalent linking of different concentrations of modified cyclodextrins was applied to the chemical surfaces by incorporating additional hydroxyl groups from the glucose monomeric unities of cyclodextrins. In this manner, variable larger-sized and inter-branched grafted gold core–shell silica nanoparticles were generated. The ultraluminescent properties were conserved due to the non-optical activity of the cyclodextrins. However, they generated enhanced ultraluminescence phenomena. Laser fluorescence microscopy nanoimaging showed enhanced resolutions in comparison to non-grafted supramolecular gold core–shell nanoparticles. The differences in their interactions and the sizes of the nanoassemblies were explained by their single nanoparticle diameters and the interacting chemical groups on their nanosurfaces. While the varied luminescence emissions generated were tuned by plasmonics, enhanced plasmonic phenomena and light scattering properties were seen depending on the type of nanoassembly. Thus, optically active and non-optically active materials led to different optical properties in the bright field and enhanced the excited state within the electromagnetic near-field of the gold nanotemplates. In this manner, it was possible to achieve high sensitivity by varying the spacer lengths and optical properties. Therefore, further perspectives regarding the design of nano-tools composed of light for various applications were discussed.

Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies

BackgroundBased on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment.MethodsGold-core/silica-shell nanoparticles embedding a water-soluble iridium(III) complex as photosensitizer and luminescent probe (Iren-AuSiO2_COOH) were efficiently decorated with amino-terminated EGFR (CL4) and PDGFRβ (Gint4.T) aptamers (Iren-AuSiO2_Aptamer). The targeting specificity, and the synergistic photodynamic and photothermal effects of either single- and dual-aptamer-decorated nanoparticles have been assessed by confocal microscopy and cell viability assays, respectively, on different human cell types including mesenchymal subtype triple-negative breast cancer (MES-TNBC) MDA-MB-231 and BT-549 cell lines (both EGFR and PDGFRβ positive), luminal/HER2-positive breast cancer BT-474 and epidermoid carcinoma A431 cells (only EGFR positive) and adipose-derived mesenchymal stromal/stem cells (MSCs) (only PDGFRβ positive). Cells lacking expression of both receptors were used as negative controls. To take into account the tumor-stroma interplay, fluorescence imaging and cytotoxicity were evaluated in preclinical three-dimensional (3D) stroma-rich breast cancer models.ResultsWe show efficient capability of Iren-AuSiO2_Aptamer nanoplatforms to selectively enter into target cells, and kill them, through EGFR and/or PDGFRβ recognition. Importantly, by targeting EGFR+ tumor/PDGFRβ+ stromal cells in the entire tumor bulk, the dual-aptamer-engineered nanoparticles resulted more effective than unconjugated or single-aptamer-conjugated nanoparticles in either 3D spheroids cocultures of tumor cells and MSCs, and in breast cancer organoids derived from pathologically and molecularly well-characterized tumors.ConclusionsOur study proposes smart, novel and safe multifunctional nanoplatforms simultaneously addressing cancer-stroma within the tumor microenvironment, which are: (i) actively delivered to the targeted cells through highly specific aptamers; (ii) localized by means of their luminescence, and (iii) activated via minimally invasive light, launching efficient tumor death, thus providing innovative precision therapeutics. Given the unique features, the proposed dual targeted nanoformulations may open a new door to precision cancer treatment.

Superparamagnetic Core–Mesoporous Silica Shell Nanoparticles with Tunable Extra- and Intracellular Dissolution Rates

Superparamagnetic Core–Mesoporous Silica Shell Nanoparticles with Tunable Extra- and Intracellular Dissolution Rates

Synergistically Enhancing Immunotherapy Efficacy in Glioblastoma with Gold-Core Silica-Shell Nanoparticles and Radiation.

Glioblastoma is a highly aggressive brain tumor with universally poor outcomes. Recent progress in immune checkpoint inhibitors has led to increased interest in their application in glioblastoma. Nonetheless, the unique immune milieu in the brain has posed remarkable challenges to the efficacy of immunotherapy. We aimed to leverage the radiation-induced immunogenic cell death to overcome the immunosuppressive network in glioblastoma. We developed a novel approach using the gold-core silica-shell nanoparticles (Au@SiO2 NPs) in combination with low-dose radiation to enhance the therapeutic efficacy of the immune checkpoint inhibitor (atezolizumab) in brain tumors. The biocompatibility, immune cell recruitment, and antitumor ability of the combinatorial strategy were determined using in vitro assays and in vivo models. Our approach successfully induced the migration of macrophages towards brain tumors and promoted cancer cell apoptosis. Subcutaneous tumor models demonstrated favorable safety profiles and significantly enhanced anticancer effects. In orthotopic brain tumor models, the multimodal therapy yielded substantial prognostic benefits over any individual modalities, achieving an impressive 40% survival rate. In summary, the combination of Au@SiO2 NPs and low-dose radiation holds the potential to improve the clinical efficacy of immune checkpoint inhibitors. The synergetic strategy modulates tumor microenvironments and enhances systemic antitumor immunity, paving a novel way for glioblastoma treatment.

Dark cytotoxicity beyond photo-induced one of silica nanoparticles incorporated with RuII nitrosyl complexes and luminescent {Mo6I8} cluster units

The present work reports the synthesis of the silica nanoparticles (SNs) incorporated by two photoactive components, which are the representatives of RuII nitrosyl complexes and [{Mo6I8}(CH3COO)6]2− cluster units. The RuII nitrosyl complexes are incorporated through the doping procedure into the SNs. The embedding of amino-groups onto the RuII-doped SNs facilitates the deposition of the cluster units, thus, resulting in the heterometallic core–shell SNs. Combination of the two photoactive components in the SNs results in the anti-synergistic effect on the photochemical and photodynamic activities of the RuII and {Mo6I8}-based complexes correspondingly. The enhanced leaching of the cluster units from the heterometallic SNs correlates with the nitrosyl → nitro transformation of the encapsulated RuII nitrosyl complexes. The formation of the so-called protein corona onto the heterometallic SNs is revealed as the reason for high colloid stability and efficient cell internalization, which is visualized through the red emission of the {Mo6I8}-clusters. The cytotoxicity measurements reveal both synergistic effect of both components on the cytotoxicity evaluated in the so-called dark conditions and anti-synergistic effect on the photo-induced cytotoxicity. The significant dark cytotoxicity of the heterometallic SNs correlates with their high internalization and the enhanced leaching of the cluster units.

Surface fabrication of magnetic core-shell silica nanoparticles with perylene diimide as a fluorescent dye for nucleic acid visualization

• Design and synthesis of non-toxic and economic magnetic nanoparticle colorant dye for nucleic acid visualization. • Development dual-functional nanoparticle have strong magnetic properties and intense fluorescent light. • Evaluation of particle adsorption loading efficiency and their release of nucleic acid. • The magnetic dye can be easy recovered and controlled their movement by applying external magnetic. Up to date most traditional fluorescent dyes that serve to detect nucleic acids in a selective manner face growing environmental and economic challenges due to their high toxicity, expensiveness, the long staining times required and the low sensitivities. Further attention went to replace the current widely used ethidium bromide (EB) by more safe and stable dyes but still some of the above drawbacks persist. In this work an innovative fluorescent dye has been designed and synthesized via impregnating perylene diimide into the functionalized surface of magnetic core–shell silica nanoparticles. One of the free hydroxyl groups on the perylene diimide enables the colored magnetic nanoparticles to easily disperse in water and their movement can be controlled with magnetism which allow the separation after their used. These particles are of low toxicity, environmentally friendly and have high sensitivity. Fluorescent properties and molecular interaction were studied. The designed particles show high DNA binding capacity which makes the developed particle promising for DNA extraction, delivery and fluorescent labeling. Theoretical studies confirm that the dye is placed between two DNA base pair similar with pervious observation with EB and the distance was less than 6 Å which is much less than the distance of EB dye interaction (15 Å) as reported before [1] .

Magnetic Core-Shell Iron Oxides-Based Nanophotocatalysts and Nanoadsorbents for Multifunctional Thin Films.

In recent years, iron oxides-based nanostructured composite materials are of particular interest for the preparation of multifunctional thin films and membranes to be used in sustainable magnetic field adsorption and photocatalysis processes, intelligent coatings, and packing or bio-medical applications. In this paper, superparamagnetic iron oxide (core)-silica (shell) nanoparticles suitable for thin films and membrane functionalization were obtained by co-precipitation and ultrasonic-assisted sol-gel methods. The comparative/combined effect of the magnetic core co-precipitation temperature (80 and 95 °C) and ZnO-doping of the silica shell on the photocatalytic and nano-sorption properties of the resulted composite nanoparticles were investigated by ultraviolet-visible (UV-VIS) spectroscopy monitoring the discoloration of methylene blue (MB) solution under ultraviolet (UV) irradiation and darkness, respectively. The morphology, structure, textural, and magnetic parameters of the investigated powders were evidenced by scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, Brunauer–Emmett–Teller (BET) measurements, and saturation magnetization (vibrating sample magnetometry, VSM). The intraparticle diffusion model controlled the MB adsorption. The pseudo- and second-order kinetics described the MB photodegradation. When using SiO2-shell functionalized nanoparticles, the adsorption and photodegradation constant rates are three–four times higher than for using starting core iron oxide nanoparticles. The obtained magnetic nanoparticles (MNPs) were tested for films deposition.

Spatially Resolved, Error‐Robust Multiplexed MicroRNA Profiling in Single Living Cells

Simultaneous imaging of multiple microRNAs (miRNAs) in individual living cells is challenging due to the lack of spectrally distinct encoded fluorophores and non-cytotoxic methods. We describe a multiplexed error-robust combinatorial fluorescent label-encoding method, termed fluorophores encoded error-corrected labels (FluoELs), enabling multiplexed miRNA imaging in living cells with error-correcting capability. The FluoELs comprise proportional dual fluorophores for encoding and a constant quantitative single fluorophore for error-corrected quantification. Both are embedded in 260 nm core–shell silica nanoparticles modified with molecular beacon detection probes. The FluoELs are low cytotoxic and could accurately quantify and spatially resolve nine breast-cancer-related miRNAs and evaluate their coordination. The FluoELs enabled a single-cell analysis platform to evaluate miRNA expression profiles and the molecular mechanisms underlying miRNA-associated diseases.

Electron-phonon effects on the photoacoustic response of gold core-silica shell nanoparticles: From the linear regime to nanocavitation.

Coating gold nanostructures with a silica shell has been long considered for biomedical applications, including photoacoustic imaging. Recent experimental and modeling investigations reported contradicting results concerning the effect of coating on the photoacoustic response of gold nanostructures. Enhanced photoacoustic response is generally attributed to facilitated heat transfer at the gold/silica/water system. Here, we examine the photoacoustic response of gold core-silica shell nanoparticles immersed in water using a combination of the two temperature model and hydrodynamic phase field simulations. Here, of particular interest is the role of the interfacial coupling between the gold electrons and silica shell phonons. We demonstrate that as compared to uncoated nanoparticles, photoacoustic response is enhanced for very thin silica shells (5nm) and short laser pulses, but for thicker coatings, the photoacoustic performance are generally deteriorated. We extend the study to the regime of nanocavitation and show that the generation of nanobubbles may also play a role in the enhanced acoustic response of core-shell nanoparticles. Our modeling effort may serve as guides for the optimization of the photoacoustic response of heterogeneous metal-dielectric nanoparticles.

Surface plasmon resonance aptasensor for soluble ICAM-1 protein in blood samples.

Intercellular Adhesion Molecule-1 (ICAM-1) is considered to be a cancer biomarker in the assessment of metastatic potential in patients and an early indicator of atherosclerosis. A labelless biosensor based on the surface plasmon resonance (SPR) signal from the specific affinity interaction of an aptamer and a soluble ICAM-1 protein was developed for blood samples. The developed aptasensor provided real-time information on the concentration of the ICAM-1 protein in blood when integrated to a purification step based on a magnetic pull-down separation. The SPR aptasensor was highly specific with a limit of detection of 1.4/0.2 ng ml-1, which was achieved through aptamer-functionalized silica-coated magnetic nanoparticles.

Sugar based cationic magnetic core-shell silica nanoparticles for nucleic acid extraction.

Nucleic acid (NA) extraction is an essential step in molecular testing for a wide range of applications. Conventional extraction protocols usually suffer from time consuming removal of non-nucleic acid impurities. In this study, a new magnetic nanoparticle (MNP) is presented to simplify the NA extraction. A core–shell design, comprising of a ferromagnetic core coated with mesoporous silica, forms the basis of the functional nanoparticle. Chemical functionalization of the silica coating includes a multistep synthesis, in which an activated nanoparticle is coupled with a triethylene glycol spaced glycosyl imidazole. The molecular design aims for charge interactions between the imidazolium-based positive nanoparticle surface and nucleic acids, with specific hydrogen bonding between the surface bonded carbohydrate and nucleic acid targets to ensure nucleic acid selectivity and avoid protein contamination. Two different carbohydrates, differing in molecular size, were selected to compare the efficiency in terms of NA extraction. A triethylene glycol spacer provides sufficient flexibility to remove particle surface constraints for the interaction. The Brunauer–Emmett–Teller (BET) analysis shows a significantly larger surface area for the disaccharide-based particles NpFeSiImMalt (∼181 m2 g−1) compared to the monosaccharide analogue NpFeSiImGlc (∼116 m2 g−1) at small particles sizes (range ∼ 15 nm) and sufficient magnetization (29 emu g−1) for easy isolation by an external magnetic field. The particles enabled a high DNA particle loading ratio of 30–45 wt% (MNP/DNA ratio), reflecting an efficient extraction process. A high desorption rate (7 min) with more than 86% of unchanged DNA loading was recorded, indicating low damage to the target extract.

Bimatoprost-Loaded Silica Shell-Coated Nanoparticles-Laden Soft Contact Lenses to Manage Glaucoma: In Vitro and In Vivo Studies.

Currently, glaucoma is managed by frequent instillation of bimatoprost eye drop therapy, which showed very poor ocular bioavailability. Contact lens is widely used as medical device to improve the drug retention on the ocular tissues. However, the traditional methods of drug loading in the contact lens matrix showed high burst release and changes the optophysical properties of the contact lens material. In this paper, a novel bimatoprost-loaded silica shell nanoparticles-laden soft contact lenses were developed to achieve sustain drug delivery without altering the optophysical properties of the contact lens. Silica-shell nanoparticles were prepared using octyltrimethoxysilane (OTMS) and microemulsion. Traditional soaking method (SM-BT), direct bimatoprost loading method (DL-BT), and microemulsion-laden contact lens (ME-BT) were developed for comparison. The silica shell-coated nanoparticles-laden soft contact lenses (SiS-BT) showed improved swelling, transmittance, oxygen permeability, and lysozyme adherence compared to SM-BT, DL-BT, and ME-BT lenses. The DL-BT and ME-BT batch showed high bimatoprost lost/leaching during extraction and sterilization steps, with low cumulative drug release. Also, SiS-BT lens showed sustain bimatoprost release for 96 h. In a rabbit tear fluid model, the SiS-BT lens showed high bimatoprost concentration for 72 h compared to ME-BT lens and eye drop therapy. Based on histopathological studies of cornea, the SiS-BT lens was found to be safe for human applications. The data demonstrated the novel application of silica shell nanoparticles to deliver bimatoprost from the contact lens for extended period of time without altering the optophysical properties of the contact lens.

Hydrophobic Drug Release Studies from the Core/Shell Magnetic Mesoporous Silica Nanoparticles and their Anticancer Application

Multiple therapeutic hydrophobic drugs can be delivered simultaneously by inorganic, biocompatible iron core mesoporous silica shell nanoparticles. We synthesized superparamagnetic iron oxide nanocrystals encapsulated within mesostructured silica spheres through the sol-gel process. The dose of hydrophobic drugs Paclitaxel (PTX) and Camptothecin (CPT) loading and released on Fe3 O4 @SiO2 core/shell nanoparticle detected by U.V-visible spectrophotometry using a platform of nanoparticles (NPS). After being subjected to external heating, the drug release efficiency of paclitaxel (PTX) and camptothecin (CPT) Fe3 O4 @SiO2 core/shell nanoparticles is increased. Paclitaxel (PTX) and Camptothecin (CPT) Fe3 O4 @SiO2 core/shell nanoparticles did not heat the solution when an alternating magnetic field (AMF) was applied, and there was only mild drug leakage. When compared to Fe3 O4 @MSNs, the nanoparticles (PTX) and (CPT) Fe3 O4 @MSNs function as cancer-targeting mediators, increasing the killing of PANC-1 cancer cells. Human cancer cells were given these therapeutic anticancer water-insoluble drugs with nanoparticles, which is a valuable vehicle for drug delivery, and induced the inhibition of proliferation. Therefore, the goal of this study to emphasize Fe3 O4 @SiO2 core/shell potential as a superior candidate for hydrophobic drug delivery to the PANC-1 cancer cell.

In Vivo Tracking of the Degradation of Mesoporous Silica through 89 Zr Radio-Labeled Core-Shell Nanoparticles.

While mesoporous silica nanoparticles (MSNs) are extensively studied as high-potential drug delivery platforms, the successful clinical translation of these nanocarriers strongly depends on their biodistribution, biodegradation, and elimination patterns in vivo. Here, a novel method is reported to follow the in vivo degradation of MSNs by tracking a radioactive label embedded in the silica structure. Core-shell silica nanoparticles (NPs) with a dense core and a mesoporous shell are labeled with low quantities of the positron emitter 89 Zr, either in the dense core or in the mesoporous shell. In vivo positron emission tomography imaging and ex vivo organ measurements reveal a remarkable difference in the 89 Zr biodistribution between the shell-labeled and the core-labeled NPs. Release of the radiotracer from shell-labeled NPs is used as a probe of the extent of silica dissolution, and a prompt release of the radioisotope is observed, with partial excretion already in the first 2 h post injection, and a slower accumulation in bones over time. On the other hand, when 89 Zr is embedded in the nanoparticle core, the biodistribution remains largely unchanged during the first 6 h. These findings indicate that MSNs have fast, hour-scale, degradation kinetics in vivo.

Dye-Doped Silica Nanoparticles for Enhanced ECL-Based Immunoassay Analytical Performance

Electrochemiluminescence (ECL) is a leading technique in bioanalysis.[1] It is a luminescent phenomenon where the excited species are produced with an electrochemical stimulus rather than with a light excitation source. For this reason, ECL displays improved signal-to-noise ratio compared to photoluminescence, with minimized effects due to light scattering and luminescence background.[2]Chasing ever-increasing sensitivities, ECL can ideally be coupled to nanotechnology to develop new strategies for clinical applications and analyte determination also in real and complex matrices.[3] In particular, dye-doped silica nanoparticles (DDSNs) present many advantages: they can be easily synthesized, are hydrophilic and are prone to bioconjugation thanks to silica chemistry. With this approach we were able to achieve extremely bright systems and DDSNs allow the 8.5 fold increase of ECL intensity.[4] In DDSNs, light emission is influenced by the combination of several factors that make DDSNs complex multichromophoric structures. However, when ECL comes into play, the scenario is even more complicated due to the coreactant−NP interactions effect. Such complex scenario was approached at the theoretical level by developing suitable mechanistic models for ECL generation[5] while, at the same time, the influence of doping level on ECL efficiency was evaluated. Our results showed that the ECL intensity of a nanosized system cannot be merely incremented acting on doping, since other parameters come into play. These studies support the application in ECL microscopy providing valuable indications for the design of more efficient ECL nano- and micro-sized labels towards more sensitive ECL-based immunoassay for bioanalysis applications. [6]References[1] W. Miao, “Electrogenerated Chemiluminescence and Its Biorelated Applications”, Chem. Rev., 2008, vol. 108, pp. 2506–2553.[2] Z. Liu, W. Qi, G. Xu, “Recent advances in electrochemiluminescence”, Chem. Soc. Rev., 2015, vol. 44, pp. 3117–3142.[3] C. Ma, Y. Cao, X. Gou, J. J. Zhu, “Recent progress in electrochemiluminescence sensing and imaging”, Anal. Chem., 2015, vol. 92, pp. 431-454.[4] G. Valenti, E. Rampazzo, S. Bonacchi, L. Petrizza, M. Marcaccio, M. Montalti, L. Prodi, F. Paolucci, “Variable Doping Induces Mechanism Swapping in Electrogenerated Chemiluminescence of Ru(bpy) 3 2+ Core–Shell Silica Nanoparticles”, J. Am. Chem. Soc., 2016, vol. 138, pp. 15935–15942.[5] E. Daviddi, A. Oleinick, I. Svir, G. Valenti, F. Paolucci, C. Amatore, “Theory and Simulation for Optimising Electrogenerated Chemiluminescence from Tris(2,2′-bipyridine)-ruthenium(II)-Doped Silica Nanoparticles and Tripropylamine”, ChemElectroChem, 2017, vol. 4, pp. 1719–1730.[6] A. Zanut, F. Palomba, M. Rossi Scota, S. Rebeccani, M. Marcaccio, D. Genovese, E. Rampazzo, G. Valenti, F. Paolucci, L. Prodi, "Dye‐Doped Silica Nanoparticles for Enhanced ECL‐Based Immunoassay Analytical Performance", Angew. Chemie Int. Ed., 2020, vol. 132, pp. 22042-22047 Figure 1

Combinatorial delivery of doxorubicin and acridine orange by gold core silica shell nanospheres functionalized with poly(ethylene glycol) and 4-methoxybenzamide for cancer targeted therapy

Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' therapeutic selectivity and efficacy. Gold core silica shell (AuMSS) nanoparticles present physicochemical properties that allow their simultaneous application as drug delivery and imaging agents. Herein, poly(ethylene glycol) was modified with 4-methoxybenzamide and 3-(triethoxysilyl)propyl isocyanate (TPANIS) to create a novel surface functionalization capable of improving the colloidal stability and specificity of AuMSS nanospheres towards cancer cells. Moreover, a dual drug combination based on Doxorubicin (DOX) and Acridine orange (AO) was characterized and administered using the AuMSS-TPANIS nanospheres. The obtained results show that the DOX:AO drug combination can mediate a synergistic therapeutic effect in both HeLa and MCF-7 cells, particularly at the 2:1, 1:1, and 1:2 ratios. Additionally, the TPANIS functionalization increased the AuMSS nanospheres colloidal stability and selectivity towards MCF-7 cancer cells (overexpressing sigma receptors). Such also resulted in an enhanced cytotoxic effect against MCF-7 cells when administering the DOX:AO drug combination with the AuMSS-TPANIS nanospheres. Overall, the obtained results confirm the therapeutic potential of the DOX:AO drug combination as well as the targeting capacity of AuMSS-TPANIS, supporting its application in the cancer-targeted combinatorial chemotherapy.

Carminic Acid Linked to Silica Nanoparticles as Pigment/Antioxidant Bifunctional Excipient for Pharmaceutical Emulsions.

The incorporation of pigments and natural polyphenols into inorganic matrices, resulting in a hybrid material that improves the resistance and chemical stability of the pigments and the antioxidant capacity of the materials, has been of great interest to the pharmaceutical, chemical and food industries. The aim of this work was to prepare and characterize a bifunctional pigment–antioxidant nanomaterial-based carminic acid-decorated solid core-mesoporous shell silica nanoparticles, evaluating its properties as a pigment, its antioxidant capacity and its properties as a chemical stabilizer of emulsions. The chemical stability of oil-in-water (O/W) Pickering emulsions was evaluated determining the stability of vitamin E solubilized in the oil phase. Carminic acid was attached through the action of coupling ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) agents, and the resulting spherical and homogeneous nanoparticles showed a diameter close to 175 nm. A notorious change of emulsion color was observed by the addition of the nanomaterial. Emulsions showed an attractive pink color, and when the pH was adjusted to pH 3 and pH 9, a change in color was observed, analogous to carminic acid in solution. The nanomaterial incorporation also improved chemical stability, decreasing vitamin E consumption to 9.26% of the initial value, demonstrating an important antioxidant effect of the developed nanomaterial.

Gd- and Eu-Loaded Iron Oxide@Silica Core-Shell Nanocomposites as Trimodal Contrast Agents for Magnetic Resonance Imaging and Optical Imaging.

Superparamagnetic maghemite core-porous silica shell nanoparticles, γ-Fe2O3@SiO2 (FS), with 50 nm diameter and a 10 nm core, impregnated with paramagnetic complexes b-Ln ([Ln(btfa)3(H2O)2]) (where btfa = 4,4,4-trifluoro-l-phenyl-1,3-butanedione and Ln = Gd, Eu, and Gd/Eu), performing as promising trimodal T1-T2 MRI and optical imaging contrast agents, are reported. These nanosystems exhibit a high dispersion stability in water and no observable cytotoxic effects, witnessed by intracellular ATP levels. The structure and superparamagnetic properties of the maghemite core nanocrystals are preserved upon imbedding the b-Ln complexes in the shell. Hela cells efficiently and swiftly internalize the NPs into the cytosol, with no observable cytotoxicity below a concentration of 62.5 μg mL-1. These nanosystems perform better than the free b-Gd complex as T1 (positive) contrast agents in cellular pellets, while their performance as T2 (negative) contrast agents is similar to the FS. Embedding of the b-Eu complex in the silica pores endows the nanoparticles with strong luminescence properties. The impregnation of gadolinium and europium complexes in a 1:1 ratio afforded a trimodal nanoplatform performing as a luminescent probe and a double T1 and T2 MRI contrast agent even more efficient than b-Gd used on its own, as observed in cell-labeled imaging experiments and MRI cell pellets.

Synthesis and characterization of poly(N-isopropylacrylamide-co-N,N′-methylenebisacrylamide-co-acrylamide) core – Silica shell nanoparticles by using reactive surfactant polyoxyethylene alkylphenyl ether ammonium sulfate

We report a novel approach based on using polyoxyethylene alkylphenyl ether ammonium sulfate (HS10) as an anion reactive surfactant, which greatly reduced the size of poly(N-isopropylacrylamide-co-acrylamide-co-N,N′-methylenebisacrylamide) [P(NIPAM/AM/MBA)] microgel core – silica shell particles. First, the microgel cores were synthesized by copolymerization of N-isopropylacrylamide (NIPAM), N,N′-methylenebisacrylamide (MBA) with a variation of acrylamide (AM) and HS10 concentration in water. It followed by silica encapsulation of the microgel cores via the addition of 3-glycidyloxypropyltrimethoxysilane (GLYMO) and tetraethyl orthosilicate (TEOS) at alkaline environment (pH 12). It is interesting to note that the size of both PNIPAM-based microgel cores and PNIPAM-based microgel core – silica shell particles were well-controlled by using a small level of HS10. Furthermore, SEM images of the hybrid core – shell particles show the well-defined spherical morphology with monodisperse particle size distribution. As expected, HS10-containing samples are covered by the porous silica shell layer, instead of continuous silica shell obtained from HS10-free samples observed in TEM images. This novel incorporation not only well controls the core size and shell morphology, leading to increase their specific surface area but also does not greatly affect the thermo-sensitivity of final products. The resultant thermo-responsive microgel core – silica shell particles with controlled particle morphology and physicochemical properties are useful for biomedical application fields.