Core-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.

Fabrication of Rhenium Disulfide/Mesoporous Silica Core-Shell Nanoparticles for a pH-Responsive Drug Release and Combined Chemo-Photothermal Therapy.

A stimuli-responsive drug delivery nanocarrier with a core-shell structure combining photothermal therapy and chemotherapy for killing cancer cells was constructed in this study. The multifunctional nanocarrier ReS2@mSiO2-RhB entails an ReS2 hierarchical nanosphere coated with a fluorescent mesoporous silica shell. The three-dimensional hierarchical ReS2 nanostructure is capable of effectively absorbing near-infrared (NIR) light and converting it into heat. These ReS2 nanospheres were generated by a hydrothermal synthesis process leading to the self-assembly of few-layered ReS2 nanosheets. The mesoporous silica shell was further coated on the surface of the ReS2 nanospheres through a surfactant-templating sol-gel approach to provide accessible mesopores for drug uploading. A fluorescent dye (Rhodamine B) was covalently attached to silica precursors and incorporated during synthesis in the mesoporous silica walls toward conferring imaging capability to the nanocarrier. Doxorubicin (DOX), a known cancer drug, was used in a proof-of-concept study to assess the material's ability to function as a drug delivery carrier. While the silica pores are not capped, the drug molecule loading and release take advantage of the pH-governed electrostatic interactions between the drug and silica wall. The ReS2@mSiO2-RhB enabled a drug loading content as high as 19.83 mg/g doxorubicin. The ReS2@mSiO2-RhB-DOX nanocarrier's cumulative drug release rate at pH values that simulate physiological conditions showed significant pH responsiveness, reaching 59.8% at pH 6.8 and 98.5% and pH 5.5. The in vitro testing using HeLa cervical cancer cells proved that ReS2@mSiO2-RhB-DOX has a strong cancer eradication ability upon irradiation with an NIR laser owing to the combined drug delivery and photothermal effect. The results highlight the potential of ReS2@mSiO2-RhB nanoparticles for combined cancer therapy in the future.

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.

Optimization of shell-isolated nanoparticle-enhanced Raman spectroscopy experiments with silver core-silica shell nanoparticles

The synthesized silver nanoparticles (60–70 nm) coated with a thin (5–6 nm) shell of silicon dioxide were applied for the analysis of popular 4-mercaptobenzoic acid (4-MBA) self-assembled monolayer by the shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). The detailed synthesis, purification of the nanoparticles, and optimizing washing procedure are provided. The obtained results are proved by HR-TEM, UV-Vis, and SHINERS data. The report opens up a broad possibility of using core-shell nanoparticles in SHINERS experiments, avoiding lengthy purification procedures while maintaining particle stability and Raman signal intensity.

Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core-Shell Silica Nanoparticles.

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

Bi-coloured enhanced luminescence imaging by targeted switch on/off laser MEF coupling for synthetic biosensing of nanostructured human serum albumin.

In this communication luminescent bioconjugated human serum albumin nanostructures (HSA NPs) with tiny ultraluminescent gold core-shell silica nanoparticles (Au@SiO2-Fl) were designed with enhanced bi-coloured luminescence properties. The HSA NPs were obtained from Human Serum Albumin free (HSA free) through the desolvation method, and Au@SiO2-Fl, through modified Turkevich and Störber methods. In this manner, porous HSA Nanostructures of 150.0-200nm and Au@SiO2-Fl 45.0nm final diameters were obtained. Both methodologies and structures were conjugated to obtain modified Nanocomposites based on tiny gold cores of 15nm surrounded with well spatial Nanostructured architectures of HSA (d15 Au@SiO2-Fl-HSA) that generated variable nanopatterns depending on the modified methodology of synthesis applied within colloidal dispersions. Therefore, three methodologies of non-covalent conjugation were developed. In optimal conditions, through Transmission Electronic Microscopy (TEM), well resolved multilayered nano-architectures with a size 190.0-200nm in average with variable contrast depending of the focused nanomaterial within the nanocomposite were shown. Optimized nanoarchitecture was based on a template tiny gold core-shell surrounded by nanostructured HSA NPs (d15 Au@SiO2-Fl-HSA). In this manner, the NanoImaging generated by laser fluorescence microscopy permitted to record improved optical properties and functionalities, such as: (i) enhanced ultraluminescent d15 Au@SiO2-Fl-HSA composites in comparison to individual components based on Metal Enhanced Fluorescence (MEF); (ii) diminished photobleaching; (iii) higher dispersibility; (iv) higher resolution of single bright nano-emitters of 210.0nm sizes; and (v) enhanced bi-coloured Bio-MEF coupling with potential non-classical light delivery towards other non-optical active biostructures for varied applications. The characterization of these nanocomposites allowed the comparison, evaluation and discussion focused on new properties generated and functionalities based on the incorporation of different types of tuneable materials. In this context, the biocompatibility, Cargo confined spaces, protein-based materials, optical transparent could be highlighted, as well as optical active materials. Thus, the potential applications of nanotechnology to both nanomedicine and nano-pharmaceutics were discussed.

Reusable SiO2@NiO core-shell nanoparticles catalyzed efficient synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8, 13-dione derivatives

Multicomponent condensation reaction of substituted aromatic aldehydes with 2-naphthol/2,7-dihydroxynaphthalene and 2-hydroxynaphthalene-1,4-dione was catalyzed by nickel oxide supported on silica core-shell nanoparticles (SiO2@NiO) as Lewis acid catalyst in the ethanolic medium at 80 °C. The present catalytic protocol was used to synthesize diverse 14-Aryl-14H-dibenzo[a,i]xanthene-8,13-diones in good yields with a high turnover number within a short reaction time leading to good reusability with almost unchanged catalytic activity. The synthesized compounds were screened for in vitro antimicrobial activity and found to exhibit promising antibacterial and antifungal activities.

Developing core-shell silica nanoparticles to create multifunctional coating with excellent antireflection, enhanced antifogging and anticorrosion performances

How to fabricate a multifunctional coating with controllable ultralow refractive index (RI), high antifogging and anticorrosion performances by a facile method is still one of the great challenges. In this work, a simple and time-saving approach involving a microwave-assisted sol-sel process was developed to fabricate a novel core-shell structured silica nanoparticle sol by co-condensation of perfluorodecyltriethoxysilane (F-DTOS) and tetraethoxysilane (TEOS) and self-condensation of F-DTOS. Results suggest that both the co-condensations and self-condensations not only give a layer of low surface energy –C10H4F17 groups on the silica particles but also enlarge the hybrid silica particle size, providing more and larger voids to form the high porosity. After spinning the silica nanoparticles on the substrate, the obtained optical coating exhibits the controllable ultralow refractive index (RI) and outstanding transparency. The minimum RI and maximum transmittance of our developed coating is up to ~1.04 and ~100 %, respectively. Moreover, because of the high porosity and the presence of low surface energy –C10H4F17 groups in the coating, the coating has the high hydrophobicity (water contact angle ~108.8°), which not only makes it excellent antifogging performance but also affords it high-efficient anticorrosion property. After immersion in a 3.5 wt% NaCl solution for 7 days, the Rct value of the coating could be higher than 7.3 × 104 Ω cm2. It is believed that our developed method used to fabricate such multifunctional coating does not need any costly equipments, complex steps and time-consuming, making it well suited for industrial application.

Synthesis of silver nanoparticles with polyols under reflux and microwave irradiation conditions

Four polyols were used as stabilisers to synthesise silver nanospheres under reflux and microwave irradiation conditions. The nanoparticles were covered with a protective up to 10 nm silicon dioxide shell. The shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique was used to analyse the self-assembled monolayer of 4-mercaptobenzoic acid (4-MBA) by applying the produced silver core-silica shell nanoparticles. The article provides a detailed description of the synthesis, analysis and application of the nanoparticles based on UV/Vis, HR-TEM and SHINERS data.

Synthesis of amine functionalized SiO2 microspheres loaded polymeric hydrogel and its application for simultaneous eviction of divalent metal ions (Pb2+, Cd2+, Cu2+ and Ni2+)

Recovery of divalent cationic elements from aquatic system is deliberated as reconciliation of rising industrial growth and access to quality drinking water. Herein we report tactically designed amino functionalized silica core-shell nanoparticle loaded polymeric hydrogel network as benchmark sorbent for divalent metal ions (Pb2+, Cd2+, Cu2+, Ni2+). The simple fabrication method for silica core-shell microspheres involves sol-gel synthesis of the polystyrene (PS) core, afterwards the formation of the silica shell by hydrolysis and condensation reaction, and finally the dissolution of the PS core. The surface of synthesized SiO2 microspheres was amine functionalized before being impregnated within a alginate matrix of polymer to generate amino functionalized SiO2 microsphere loaded polymeric hydrogel [NH2–SiO2MS-Ca-Alg] beads. Combining functionalized silica into polymeric hydrogel structure resulted extraordinary sorption capacities for divalent metal ions [191.4, 70.7, 64.9 and 35.8 mg g−1 respectively for Pb, Cd, Cu and Ni]. Density functional theory calculations were carried out to find out binding energies, preferred binding site of all four studied ions and structural changes due to their sorption. Structural evidence derived from experimental observations corroborate with the DFT analysis and speciation diagram of the divalent metal ion species. Plausible mechanistic pathway and differential uptake of four divalent metal ions were explained based on both experimental findings and theoretical studies. Developed NH2–SiO2 MS-Ca-Alg beads offered outstanding selectivity towards four divalent cations in a single prescription, excellent employability under ambient conditions without affecting essential water quality parameters which are significant breakthroughs for sustainable water remediation applications.

Folic acid functionalised mesoporous core-shell silica nanoparticles loaded with carboplatin for lung cancer therapy

The development of versatile mesoporous silica nanomaterials (MSNSs) with suitable textural properties is essential for the targeted and precise delivery of therapeutic drugs for the treatment of various diseases. Especially, loading of highly toxic platinum-based drugs is essential to reduce their toxic side effects. However, loading platinum-based drugs such as carboplatin in high quantity in porous materials is extremely challenging owing to the high hydrophobicity and lack of functional groups for interacting with surfaces of MSNS. In this study, we report a facile synthesis of core-shell MSNS by employing a unique combination of triple surfactants - pluronic P123, cetyltrimethylammonium bromide (CTAB) and fluorocarbon-4 (FC-4) for targeted delivery of the carboplatin for the treatment of lung cancer. The highly hydrophobic FC-4 plays a vital role in tuning the self-assembly and thereby controls the size, morphology, textural properties and uniform pore size distribution of the MSNS. The optimised MSNS with the size range of 300–320 nm, uniform size distribution, high surface area and ordered structure was successfully synthesised. A high drug loading of 26.7% was achieved on both bare and amine functionalised MSNS with a steady release of up to 60% and 37%, respectively, in PBS. The targeting efficiency of the folic acid functionalised particles was established by confocal microscopy, which showed higher cellular uptake of these particles in A549 cells. The high carboplatin loading and targeting ability resulted in high cytotoxicity from the folic acid functionalised and drug-loaded MSNS samples in PC9 cells compared to non-targeted and bare MSNS samples. Overall, this study proposes a new single-step synthesis of core-shell MSNS with high drug loading capacity that can be used to deliver drugs in treating different types of cancers.

Intravital imaging of osteocyte integrin dynamics with locally injectable fluorescent nanoparticles

Osteocytes are the resident mechanosensory cells in bone. They are responsible for skeletal homeostasis and adaptation to mechanical cues. Integrin proteins play a prominent role in osteocyte mechanotransduction, but the details are not well stratified. Intravital imaging with multiphoton microscopy presents an opportunity to study molecular level mechanobiological events in vivo and presents an opportunity to study integrin dynamics in osteocytes. However, fluorescent imaging limitations with respect to excessive optical scattering and low signal to noise ratio caused by mineralized bone matrix make such investigations non-trivial. Here, we demonstrate that ultra-small and bright fluorescent core-shell silica nanoparticles (<7 nm diameter), known as Cornell Prime Dots (C'Dots), are well-suited for the in vivo bone microenvironment and can improve intravital imaging capabilities. We report validation studies for C'Dots as a novel, locally injectable in vivo osteocyte imaging tool for both non-specific cellular uptake and for targeting integrins. The pharmacokinetics of C'Dots reveal distinct sex differences in nanoparticle intracellular dynamics and clearance in osteocytes, which represents a novel topic of study in bone biology. Integrin-targeted C'Dots were used to study osteocyte integrin dynamics. To the best of our knowledge, we report here the first evidence of osteocyte integrin endocytosis and recycling in vivo. Our results provide novel insights in osteocyte biology and will open up new lines of investigation that were previously unavailable in vivo.

Iron Oxide@Mesoporous Silica Core-Shell Nanoparticles as Multimodal Platforms for Magnetic Resonance Imaging, Magnetic Hyperthermia, Near-Infrared Light Photothermia, and Drug Delivery.

The design of core-shell nanocomposites composed of an iron oxide core and a silica shell offers promising applications in the nanomedicine field, especially for developing efficient theranostic systems which may be useful for cancer treatments. This review article addresses the different ways to build iron oxide@silica core-shell nanoparticles and it reviews their properties and developments for hyperthermia therapies (magnetically or light-induced), combined with drug delivery and MRI imaging. It also highlights the various challenges encountered, such as the issues associated with in vivo injection in terms of NP-cell interactions or the control of the heat dissipation from the core of the NP to the external environment at the macro or nanoscale.

Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.

Despite advances by recently approved antibody-drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first-in-class ultrasmall (sub-8-nanometer (nm)) anti-human epidermal growth factor receptor 2 (HER2)-targeting drug-immune conjugate nanoparticle therapy. This multivalent fluorescent core-shell silica nanoparticle bears multiple anti-HER2 single-chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target-specific dual-modality imaging properties in a "hit and run" approach, this conjugate eradicated HER2-expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway-specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug-immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads.

A novel ratiometric fluorescence probe for the detection of copper (II) and silver(I) based on assembling dye-doped silica core-shell nanoparticles with gold nanoclusters.

Acreatively designed and constructed a multifunctional ratiometric fluorescence probe is reportedby assembling glutathione (GSH)-protected gold nanoclusters (AuNCs) with fluorescein-doped mesoporous silica nanoparticle (FS) for the detection of Cu2+ and Ag+ ions, which could eliminate most interferences by self-calibration. Under the excitation at 450 nm, the fluorescence connected with AuNCs can rapidly respond by quenching or enhancement, respectively, for Cu2+ and Ag+ ions, while the fluorescein isothiocyante (FITC) fluorescence served as reference with negligible change. The fluorescence intensity ratio showed good linear relationships with Cu2+ and Ag+ concentrations in the range 0.5-10 μM and 0.1-8 μM, respectively. The detection limits were as low as 140 nM and 60 nM for Cu2+ and Ag+ ions, respectively. The color change induced by fluorescent intensity ratio variation could also beemployed for visual discrimination. TheAuNC-embedded FS (FS-Au) nanoprobe was successfully used for Cu2+ and Ag+ ion determination in drinking water and intracellular Cu2+ imaging, which exhibits promising prospects in cost-effective and rapid determination of both Cu2+ and Ag+ with good sensitivity and selectivity.

Gold Nanorod–mesoporous silica core shell nanocomposites for NIR-II photothermal ablation and dual PD-L1/VEGF blockade therapy in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignancy often associated with high angiogenesis and immune suppression in the tumor microenvironment (TME). Targeting of the tumor immune microenvironment via the dual blockade of vascular endothelial growth factor (VEGF) and programmed death-ligand 1 (PD-L1) offers longer progression-free survival as a first-line treatment for patients with unresectable HCC. However, certain critical factors limit the clinical success of this therapy, including low stability of antibody, poor tumor penetration, weak immunogenicity, uncontrollable biological activity, short internal half-life, and failures in lasting antitumor immune response. Nanoparticle-based photothermal therapy (PTT) offers the possibility to amplify anti-tumor immune responses, although some issues still limit the expansion of this strategy, such as limited tumor penetration depth for the activation of immune cells and a weak immune response in a powerful immunosuppressive TME. Here, we designed a nanoplatform (GSBVVP) for combined use with PTT and dual blockade of VEGF and PD-L1 to achieve an enhanced PTT-mediated immune response for the treatment of HCC. This nanoplatform is composed of a gold nanorod/mesoporous silica core-shell nanoparticle, which demonstrated excellent photothermal conversion efficiency and could ablate tumor cells under 1208-nm laser irradiation (NIR-II). GSBVVP was loaded with a small-molecule inhibitor of PD-L1, released by NIR-II triggering. This increased the number of infiltrating CD8+ T cells via the inhibition of T cell PD-1 binding to PD-L1 on tumor cells. A peptide vaccine on the surface of GSBVVP induced anti-VEGF antibody production, thereby blocking the secretion of VEGF by tumor cells in the TME and suppressing the angiogenesis signaling pathway. Animal studies verified that GSBVVP-mediated photothermal immunotherapy significantly inhibited primary tumor growth, suppressed metastasis and prevented tumor recurrence. Our strategy of bridging photothermal ablation with dual blockade VEGF and PD-L1 by nanotechnology may have a great potential for clinical translation, and it is promising for cancer immunotherapy.

Dual-color core-shell silica nanosystems for advanced super-resolution biomedical imaging.

Fluorescent core-shell silica nanoparticles are largely employed in nanomedicine and life science thanks to the many advantages they offer. Among these, the enhancement of the stability of the fluorescent signal upon fluorophore encapsulation into the silica matrix and the possibility to combine in a single vehicle multiple functionalities, physically separated in different compartments. In this work, we present a new approach to the Stöber method as a two-cycle protocol for the tailored synthesis of dual-color fluorescent core-shell silicon dioxide nanoparticles (SiO2 NPs) using two commercial dyes as model. To facilitate the colloidal stability, the nanoparticle surface was functionalized with biotin by two approaches. The biotinylated nanosystems were characterized by several analytical and advanced microscopy techniques including Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), UV-vis, transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Moreover, advanced super-resolution based on structured illumination was used for the imaging of the double-fluorescent NPs, both on a substrate and in the cellular microenvironment, at nanometric resolution 100 nm, in view of their versatile potential employment in fluorescence optical nanoscopy as nanoscale calibration tools as well as in biomedical applications as biocompatible nanosystems for intracellular biosensing with high flexibility of use, being these nanoplatforms adaptable to the encapsulation of any couple of dyes with the desired function.

Engineered Ultrasmall Nanoparticle Drug‐Immune Conjugates with “Hit and Run” Tumor Delivery to Eradicate Gastric Cancer

AbstractDespite advances by recently approved antibody‐drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first‐in‐class ultrasmall (sub‐8‐nanometer (nm)) anti‐human epidermal growth factor receptor 2 (HER2)‐targeting drug‐immune conjugate nanoparticle therapy. This multivalent fluorescent core–shell silica nanoparticle bears multiple anti‐HER2 single‐chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties. Most surprisingly, drawing upon its favorable physicochemical, pharmacokinetic, clearance, and target‐specific dual‐modality imaging properties in a “hit and run” approach, this conjugate eradicated HER2‐expressing gastric tumors without any evidence of tumor regrowth, while exhibiting a wide therapeutic index. Therapeutic response mechanisms are accompanied by the activation of functional markers, as well as pathway‐specific inhibition. Results highlight the potential clinical utility of this molecularly engineered particle drug‐immune conjugate and underscore the versatility of the base platform as a carrier for conjugating an array of other immune products and payloads.

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] .

Bioinspired core-shell silica nanoparticles monitoring extra- and intra-cellular drug release

Förster resonance energy transfer (FRET) has been widely used for monitoring drug release from nanoparticles (NPs). To understand the drug release from bioinspired drug-core silica-shell NPs, we synthesised two types of NPs using the dual-functional peptide SurSi via biosilicification for the first time, i.e., silica NP conjugated with FRET (Cy3 and Cy5) molecules, and FRET-core (DiO and DiI) silica-shell NP with different shell thicknesses (18 and 41 nm). The release kinetics of these two types of NPs were investigated under different conditions, including fetal bovine serum (FBS) and in cells, to mimic the drug release during blood circulation and intracellularly. Two different drug release mechanisms were identified. Cargo diffusion dominated the release during circulation, while the degradation of silica shell played a key role in drug release intracellularly.