Hollow Mesoporous Nanoparticles Research Articles

Synthesis of Monodispersed Hollow Mesoporous Organosilica and Silica Nanoparticles with Controllable Shell Thickness Using Soft and Hard Templates

Hollow mesoporous nanoparticles with controllable size (less than 100 nm) are desired as drug-delivery carriers. Herein, we report the synthesis of monodispersed hollow mesoporous organosilica (HMOS) and hollow mesoporous silica (HMS) nanoparticles using soft and hard templating methods. HMOS shells, with 1,2-bis(triethoxysilyl)ethane (BTEE) as the precursor and hexadecyltrimethylammonium bromide and sodium dodecyl sulfate (SDS) as the soft templates, were formed on monodispersed silica nanoparticles (SNPs), which were used as the hard templates. HMOS and HMS nanoparticles were obtained by removing the SNPs after three rounds of ammonia dialysis. The hollow size of HMOS can be tuned by changing the size of the SNPs. By using SNPs with a size of 36.5 nm, hollow spaces of approximately 20 nm connected the surface through narrow pores (<5 nm). Mesopores of approximately 12 nm were formed by the surfactant micelles. Additionally, the interparticle space in HMOS and HMS was approximately 12 nm. The shell thicknesses of HMOS and HMS could be tuned in the range of 5-9 nm by changing the BTEE amount. Moreover, the amount of surfactant used varied the porous structure. The HMOS with a thickness of 5 nm exhibited a Brunauer-Emmett-Teller (BET) surface area of 268 m2/g and a total pore volume of 1.14 cm3/g. Meanwhile, HMS demonstrated a BET surface area of 553 m2/g and a total pore volume of 1.82 cm3/g while maintaining a hollow structure. HMOS displayed a high loading capacity for ibuprofen (3009 mg/g), and its drug release system showed a sustained-release property. Therefore, the HMOS preparation using hard and soft templates proposed herein can control the hollow size and shell thickness for drug-delivery applications.

An Magnetic-Targeting Nano-Diagnosis and Treatment Platform for TNBC.

In this experiment, we constructed a magnetic targeting nano-diagnosis and treatment platform of doxorubicin (DOX) combined with iron nanoparticles, and explored their application value and mechanism in the treatment of Triple Negative Breast Cancer (TNBC), as well as its new diagnosis and treatment mode in Magnetic Resonance Imaging (MRI). Hollow mesoporous nanoparticles (HFON) were synthesized by solvothermal method, and loaded the drug DOX (DOX@HFON) to treat TNBC. The experiments in vivo and in vitro were carried out according to the characteristics of the materials. In vitro experiments, the killing effect of the drug on cells was verified by cell viability CCK8, ROS generation level, LPO evaluation and flow cytometry; the MRI effect and targeted anti-tumor therapy effect were studied by in vivo experiments; then the tumor tissue sections were detected by Ki-67, CD31, ROS, LPO and TUNEL immunofluorescence detection; H&E staining and blood biochemical tests were used to evaluate the biosafety of the materials. Through a series of characterization tests, it is confirmed that the nano-materials prepared in this experiment have positive drug loading properties. MDA-MB-231 cells had great phagocytic ability to DOX@HFON under Confocal Laser Scanning Microscope (CLSM). Experiments in vitro confirmed that DOX and Fe were released and concentrated in cells, and a large number of ROS production and induction of LPO were detected by DCFH-DA and C11-BODIPY probes in cells. Apoptosis experiments further confirmed that DOX@HFON induced apoptosis, autophagy and ferroptosis. In the vivo experiment, the anti-tumor therapy effect of MAGNET@DOX@HFON group was the most significant, and in MRI also proved that the drug had great tendency and imaging ability in tumor tissue. The new magnetic targeting nano-diagnosis and treatment platform prepared in this experiment is expected to become a new treatment model for TNBC.

Noble-Metal-Based Hollow Mesoporous Nanoparticles: Synthesis Strategies and Applications.

As second-generation mesoporous materials, mesoporous noble metals (NMs) are of significant interest for their wide applications in catalysis, sensing, bioimaging, and biotherapy owing to their structural and metallic features. The introduction of interior hollow cavity into NM-based mesoporous nanoparticles (MNs), which subtly integrate hierarchical hollow and mesoporous structure into one nanoparticle, produces a new type of hollow MNs (HMNs). Benefiting from their higher active surface, better electron/mass transfer, optimum electronic structure, and nanoconfinement space, NM-based HMNs exhibit their high efficiency in enhancing catalytic activity and stability and tuning catalytic selectivity. In this review, recent progress in the design, synthesis, and catalytic applications of NM-based HMNs is summarized, including the findings of the groups. Five main strategies for synthesizing NM-based HMNs, namely silica-assisted surfactant-templated nucleation, surfactant-templated sequential nucleation, soft "dual"-template, Kirkendall effect in synergistic template, and galvanic-replacement-assisted surfactant template, are described in detail. In addition, the applications in ethanol oxidation electrocatalysis and hydrogenation reactions are discussed to highlight the high activity, enhanced stability, and optimal selectivity of NM-based HMNs in (electro)catalysis. Finally, the further outlook that may lead the directions of synthesis and applications of NM-based HMNs is prospected.

Novel lactoferrin-functionalized manganese-doped silica hollow mesoporous nanoparticles loaded with resveratrol for the treatment of ischemic stroke

Stroke is a central nervous system disease with a high incidence at present. It can cause pathological changes such as oxidative stress, inflammation, neuronal apoptosis, and lead to disturbance of consciousness, disability, and even death. Due to the existence of the blood-brain barrier (BBB), most of the drugs cannot reach the lesions and exert their efficacy fully. Therefore, the purpose of this research was to design a lactoferrin functionalized hollow mesoporous manganese doped silica nanoparticles (LHMMSN) for delivery of insoluble drug resveratrol (RES). The system could help insoluble drugs pass through the BBB and target inflammatory sites to exert the antioxidant stress, anti-inflammatory and neuroprotective effects. The RES was adsorbed into LHMMSN with a particle size of about 140 nm by adsorption method, and the drug loading reached 39.32 ± 2.46%. In vitro and in vivo experiments showed that LHMMSN-RES could increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce brain reactive oxygen species (ROS) and malondialdehyde (MDA) content, increase the expression of anti-inflammatory factors (IL-10) and anti-apoptotic factors (bcl-2) in brain tissue, and reduce brain tissue pro-inflammatory factors (TNF-α, IL-1β, IL-6) and pro-apoptotic factors (BAX, Cleaved caspase-3) expression. In summary, LHMMSN-RES can reduce inflammation and protect nerve cells by inhibiting oxidative stress, thereby promoting the recovery of motor function in middle cerebral artery occlusion (MCAO) model rats.

Enhanced Antimalarial Efficacy Obtained by Targeted Delivery of Artemisinin in Heparin-Coated Magnetic Hollow Mesoporous Nanoparticles.

Malaria is one of the deadliest infectious diseases threatening half of the world population. With the deterioration of the parasiticidal effect of the current antimalarials, novel approaches such as screening of more specific inhibitors and targeted delivery of drugs have been under intensive research. Herein, we prepare hollow mesoporous ferrite nanoparticles (HMFNs) of 200 nm with ferromagnetic properties using a one-pot hydrothermal reaction. A magnetically targeted drug-delivery system coloaded with artemisinin in the inner magnetite shell and heparin on the outer mesoporous shell (HMFN@ART@HEP) is developed. Specific targeting of the magnetic nanoparticles to the parasite-infected erythrocytes is achieved by the attraction between the HMFNs and hemozoin (paramagnetic), a vital metabolite of plasmodium in the erythrocytic stage. With the hemozoin production reaching the maximum during the schizont period of the parasite, HMFN@ART@HEPs are adsorbed to the infected red blood cells (iRBCs), which not only interferes with the release of merozoites but also significantly enhances the inhibitory efficacy due to the increased local concentration of artemisinin. Subsequently, the heparin coated on the surface of the nanoparticles can efficiently interfere with the invasion of freshly released merozoites to new RBCs through the specific interaction between the parasite-derived ligands and heparin, which further increases the inhibitory effect on malaria. As a cluster of heparin, heparin-coated nanoparticles provide stronger blocking capability than free heparin, resulting from multivalent interactions with surface receptors on merozoite. Thus, we have developed a HMFN-based delivery system with considerable antimalarial efficacy, which is a promising platform for treatment against malaria.

Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells.

Cancer immunotherapies, particularly therapeutic vaccination, do not typically generate robust anti-tumour immune responses. Here, we show that the intratumoral burst release of the protein annexin A5 from intravenously injected hollow mesoporous nanoparticles made of diselenide-bridged organosilica generates robust anti-tumour immunity by exploiting the capacity of primary tumours to act as antigen depots. Annexin A5 blocks immunosuppressive apoptosis and promotes immunostimulatory secondary necrosis by binding to the phagocytic marker phosphatidylserine on dying tumour cells. In mice bearing large established tumours, the burst release of annexin A5 owing to diselenide-bond cleavage under the oxidizing conditions of the tumour microenvironment and the reducing intracellular conditions of tumour cells induced systemic cytotoxic T-cell responses and immunological memory associated with tumour regression and the prevention of relapse, and led to complete tumour eradication in about 50% of mice with orthotopic breast tumours. Reducing apoptosis signalling via in situ vaccination could be a versatile strategy for the generation of adaptive anti-tumour immune responses.

Precision Cancer Theranostic Platform by In Situ Polymerization in Perylene Diimide-Hybridized Hollow Mesoporous Organosilica Nanoparticles.

Phototheranostics refers to advanced photonics-mediated theranostic methods for cancer and includes imaging-guided photothermal/chemotherapy, photothermal/photodynamic therapy, and photodynamic/chemotherapy, which are expected to provide a paradigm of modern precision medicine. In this regard, various phototheranostic drug delivery systems with excellent photonic performance, controlled drug delivery/release, and precise photoimaging guidance have been developed. In this study, we reported a special "in situ framework growth" method to synthesize novel phototheranostic hollow mesoporous nanoparticles by ingenious hybridization of perylene diimide (PDI) within the framework of small-sized hollow mesoporous organosilica (HMO). The marriage of PDI and HMO endowed the phototheranostic silica nanoparticles (HMPDINs) with largely amplified fluorescence and photoacoustic signals, which can be used for enhanced fluorescence and photoacoustic imaging. The organosilica shell can be chemically chelated with isotope 64Cu for positron emission tomography imaging. Moreover, in situ polymer growth was introduced in the hollow structure of the HMPDINs to produce thermosensitive polymer (TP) in the cavity of HMPDINs to increase the loading capacity and prevent unexpected leakage of the hydrophobic drug SN38. Furthermore, the framework-hybridized PDI generated heat under near-infrared laser irradiation to trigger the deformation of TP for controlled drug release in the tumor region. The fabricated hybrid nanomedicine with organic-inorganic characteristic not only increases the cancer theranostic efficacy but also offers an attractive solution for designing powerful theranostic platforms.

Improved in vivo tumor therapy via host-guest complexation.

In order to improve the effectiveness of cancer therapy and reduce the adverse effects of conventional chemotherapy, the development of less toxic, biocompatible, decomposable and pH-responsive nano-containers is of great importance. In this work a novel nano-container is designed and synthesized by doping a water-soluble pillar[5]arene WP5 onto hollow mesoporous silica nanoparticles (HMNPs) via host-guest complexation. This nano-container decomposes into small water-soluble fragments to achieve a highly efficient release of the loaded anticancer drug doxorubicin. Importantly, the complexation of WP5 molecules with HMNPs significantly improves the inhibition of tumor growth in vivo with minimal side effects, which can be attributed to the pH-responsiveness of the host-guest interactions. Under the extracelluar conditions, the host-guest complexation between WP5 and HMNPs enhances the loading of doxorubicin molecules. However, this host-guest complexation is prohibited under the low pH conditions in intracellular lysosomes, so that doxorubicin is released readily from the vector. The present novel drug delivery system demonstrates the great potential of host-guest complexation for cancer therapy improvement.

Facile fabrication of hollow mesoporous Eu3+-doped Gd2O3 nanoparticles for dual-modal imaging and drug delivery

In this paper, we report a facile and reproducible approach to prepare Eu3+-doped gadolinium oxide (Gd2O3) hollow mesoporous nanoparticles (HMNPs) by using polyacrylic acid sodium salt (PAAS) NPs as templates. The synthesized NPs are well-dispersed with a diameter of 120 nm and a wall thickness around 20 nm, which were utilized as nanoprobes for simultaneous dual-modal fluorescence and magnetic resonance (MR) imaging and drug delivery due to their excellent luminescent property and obvious T1-enhancement effect as well as the HM structure. The Eu3+-doped Gd2O3 HMNPs possess the loading capacity for doxorubicin (DOX) as high as 310 μg mg−1 and display the pH-responsive drug release property. In vitro cell cytotoxicity tests on cancer cells verify that the DOX loaded Eu3+-doped Gd2O3 HMNPs have comparable cytotoxicity with free DOX at the same concentration of DOX, while Eu3+-doped Gd2O3 HMNPs alone show no obvious cytotoxicity. In addition, Eu3+-doped Gd2O3 HMNPs exhibit excellent capability in dual-modal fluorescence and MR imaging. Taken together, these findings highlight the fascinating features of Eu3+-doped Gd2O3 HMNPs as dual-modal imaging contrast agents and drug delivery vehicles.

Engineering of Hollow Mesoporous Nanoparticles for Biomedical Applications

Engineering of Hollow Mesoporous Nanoparticles for Biomedical Applications

Lanthanide-based hollow mesoporous nanoparticles: a novel multifunctional platform for simultaneous gene delivery and cell imaging

GdPO4:Eu hollow spheres (denoted as GdPO4:Eu HMNs) with large pore channels in the shell have been designed as gene carriers while simultaneously acting as dual-mode bio-imaging probes.

Measurement of Uptake and Release Capacities of Mesoporous Silica Nanoparticles Enabled by Nanovalve Gates

The uptake and release capacities of mesoporous silica particles are measured on nanovalve-gated stimulated release systems, using a water soluble biological stain, Hoechst 33342, as the cargo model. Five different types of mesoporous silica nanoparticles: 2D-hexagonal MCM-41, swollen pore MCM-41, rod-like MCM-41, hollow mesoporous nanoparticles and radial mesoporous nanoparticles are studied and compared. Solid silica nanoparticles are used as the control. Because of the presence of the nanovalves, the loaded and capped particles can be washed thoroughly without losing the content of the mesopores. The quantity of Hoechst 33342 molecules trapped within the nanoparticles and released upon opening the nanovalves are systematically studied for the first time. The loading conditions are optimized by varying the Hoechst concentration in the loading solutions. Surprisingly, increasing the Hoechst concentration in the loading solution does not always result in a larger amount of Hoechst being trapped and released. Among the five types of mesoporous silica nanoparticles, the radial mesoporous nanoparticles and the swollen pore MCM-41 particles show the highest and lowest release capacity, respectively. The uptake capacities is correlated with the specific surface area of the materials rather than their internal volume. The uptake and release behaviors are also affected by charge and spatial factors.