Elastic Nanovaccine Enhances Dendritic Cell-Mediated Tumor Immunotherapy.

Nanovaccine-based immunotherapy (NBI) has the ability to initiate dendritic cell (DC)-mediated tumor-specific immune responses and maintain long-term antitumor immune memory. To date, the mechanism by which the mechanical properties of nanoparticles alter the functions of DCs in NBI remains largely unclear. Here, a soft mesoporous organosilica-based nanovaccine (SMONV) is prepared and the elasticity-dependent effect of the nanovaccine on the underlying DC-mediated immune responses is studied. It is found that the elasticity results in greater internalization of SMONV by DCs, followed by the induction of substantial cytosolic delivery of antigens via endosomal escape, leading to effective DC maturation and antigen cross-presentation. Impressively, elasticity enables SMONV to enhance lymphatic drainage of antigens in vivo, thus stimulating robust humoral and cellular immunity. The results from therapeutic tumor vaccination further reveal that subcutaneously administered SMONV effectively suppresses tumor growth in tumor-bearing mice by evoking antigen-specific CD8+ T-cell immune responses, mitigating regulatory T-cell-mediated immunosuppression, and increasing central memory and effector memory T-cell populations. Furthermore, combinatorial immunization with SMONV and anti-PD-L1 blocking antibodies results in an amplified therapeutic effect on tumor-bearing mice. These findings reveal the elastic effect of the nanovaccine on DC-mediated immune responses, and the prepared SMONV represents a facile and powerful strategy for antitumor immunotherapy.

Deformable Hollow Periodic Mesoporous Organosilica Nanocapsules for Significantly Improved Cellular Uptake.

Mesoporous solids have been widely used in various biomedical areas such as drug delivery and tumor therapy. Although deformability has been recognized as a prime important characteristic influencing cellular uptake, the synthesis of deformable mesoporous solids is still a great challenge. Herein, deformable thioether-, benzene-, and ethane-bridged hollow periodic mesoporous organosilica (HPMO) nanocapsules have successfully been synthesized for the first time by a preferential etching approach. The prepared HPMO nanocapsules possess uniform diameters (240-310 nm), high surface areas (up to 878 m2·g-1), well-defined mesopores (2.6-3.2 nm), and large pore volumes (0.33-0.75 m3·g-1). Most importantly, the HPMO nanocapsules simultaneously have large hollow cavities (164-270 nm), thin shell thicknesses (20-38 nm), and abundant organic moiety in the shells, which endow a lower Young's modulus (EY) of 3.95 MPa than that of solid PMO nanoparticles (251 MPa). The HPMOs with low EY are intrinsically flexible and deformable in the solution, which has been well-characterized by liquid cell electron microscopy. More interestingly, it is found that the deformable HPMOs can easily enter into human breast cancer MCF-7 cells via a spherical-to-oval morphology change, resulting in a 26-fold enhancement in cellular uptake (43.1% cells internalized with nanocapsules versus 1.65% cells with solid counterparts). The deformable HPMO nanocapsules were further loaded with anticancer drug doxorubicin (DOX), which shows high killing effects for MCF-7 cells, demonstrating the promise for biomedical applications.

Facile Synthesis of Yolk-Shell-Structured Triple-Hybridized Periodic Mesoporous Organosilica Nanoparticles for Biomedicine.

The synthesis of mesoporous nanoparticles with controllable structure and organic groups is important for their applications. In this work, yolk-shell-structured periodic mesoporous organosilica (PMO) nanoparticles simultaneously incorporated with ethane-, thioether-, and benzene-bridged moieties are successfully synthesized. The preparation of the triple-hybridized PMOs is via a cetyltrimethylammonium bromide-directed sol-gel process using mixed bridged silsesquioxanes as precursors and a following hydrothermal treatment. The yolk-shell-structured triple-hybridized PMO nanoparticles have large surface area (320 m(2) g(-1) ), ordered mesochannels (2.5 nm), large pore volume (0.59 cm(3) g(-1) ), uniform and controllable diameter (88-380 nm), core size (22-110 nm), and shell thickness (13-45 nm). In vitro cytotoxicity, hemolysis assay, and histological studies demonstrate that the yolk-shell-structured triple-hybridized PMO nanoparticles have excellent biocompatibility. Moreover, the organic groups in the triple-hybridized PMOs endow them with an ability for covalent connection of near-infrared fluorescence dyes, a high hydrophobic drug loading capacity, and a glutathione-responsive drug release property, which make them promising candidates for applications in bioimaging and drug delivery.

A Facile Multi-interface Transformation Approach to Monodisperse Multiple-Shelled Periodic Mesoporous Organosilica Hollow Spheres.

The synthesis of well-defined and complex hollow structures via a simple method is still a major challenge. In this work, a facile and controllable "multi-interface transformation" approach for preparation of monodisperse multi-shelled periodic mesoporous organosilica (PMO) hollow spheres has been established by a one-step hydrothermal treatment of successively grown organosilica particles. The multi-shelled PMO hollow spheres have inorganic-organic hybrid frameworks, controllable number (1-4) of shells, high surface area (∼805 m(2)/g), accessible ordered mesochannels (∼3.2 nm), large pore volume (1.0 cm(3)/g), and uniform and tunable diameter (300-550 nm), chamber size (4-54 nm), and shell thickness (10-30 nm). In addition, various organic groups (alkyl, aromatic, and heteroelement fragments) are successfully incorporated into the multi-shelled PMO hollow spheres by successively adding different bridged organosilica precursors. Notably, the distribution of different kinds of organic groups in the multi-shelled PMO hollow spheres can be precisely controlled, showing great potential for future applications. We propose that the formation of the multi-shelled PMO hollow structures is ascribed to the creation of multiple highly cross-linked organosilica interfaces, providing a new and interesting fundamental principle for PMO materials. Due to their unique structure and frameworks, triple-shelled ethane-bridged PMO hollow spheres were successfully loaded with an anti-cancer drug doxorubicin and perfluoropentane gas, which present excellent effects in the killing of cancer cells and ultrasound imaging. It is expected that the multi-interface transformation strategy provides a simple, controllable, versatile, and template-free method for preparation of various multifunctional PMOs for different applications.

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

Dual-Stimuli-Responsive Gut Microbiota-Targeting Nitidine Chloride-CS/PT-NPs Improved Metabolic Status in NAFLD.

Background and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease. Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing. Results: The nanoparticles prepared in this study have an average particle size of (255.9±5.10) nm, with an encapsulation rate of (72.83±2.13) % and a drug loading of (4.65±0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice. Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.

Gadolinium-hybridized mesoporous organosilica nanoparticles with high magnetic resonance imaging performance for targeted drug delivery.

Magnetic resonance (MR) imaging techniques, which can provide images with excellent anatomical detail, are widely used in clinical diagnosis. However, the current clinical small molecule gadolinium (Gd) contrast agents have the defects of relatively low sensitivity and poor tumor-target specificity, preventing their adoption in biology and medicine. Herein, a facile synthetic strategy to fabricate gadolinium-hybridized mesoporous organosilica nanoparticles (MOSG) through a nanoprecipitation reaction, with the surface of nanoparticles grafted with the fluorescent dye isothiocyanate (FITC) and arginine-glycine-aspartic acid (RGD) for delivery of the antitumour drug doxorubicin hydrochloride (DOX), resulting in a high-performance nanotheranostic (RGD-MOSG-FITC/DOX) for targeted magnetic resonance imaging and chemotherapy of tumors. The prepared MOSG had a particle size of 60-80 nm and gadolinium elements were distributed in clusters that exhibited boosted longitudinal relaxivity. Routine blood tests and histopathology indicated good biocompatibility of MOSG. Furthermore, after being decorated with Arg-Gly-Asp peptide (RGD), RGD-MOSG-FITC demonstrated more preferable cellular uptake by HeLa cells (high expression of αⅤß3) than MOSG without RGD grafting. Additionally, the tumor growth inhibition effect of RGD-MOSG-FITC/DOX was substantially more effective than that of the other groups. Therefore, this new delivery platform has good application potential in the field of tumor diagnosis and treatment.

Novel Synergistic Process of Impurities Extraction and Phophogypsum Crystallization Control in Wet-Process Phosphoric Acid.

Phosphogypsum, as a byproduct of wet-process phosphoric acid reaction, has caused many environmental pollution problems. To improve the property and purity of phosphogypsum in the wet-process phosphoric acid process, a liquid-solid-liquid three-phase acid hydrolysis synergistic extraction reaction system was established by adding a certain amount of extractant in the actual production process. In order to study the extraction effect and residue of impurities in the reaction system, the phase, morphology, and impurity occurrences of phosphogypsum were systematically analyzed. The results showed that when the reaction time was 7 h, the reaction temperature was 80 °C, the reaction speed was 200 r/min, the volume ratio of the extractant to diluent (dilution ratio) was 1:4 and the volume ratio of the oil phase/aqueous phase (O/A ratio) was 1:1, P2O5 conversion was the highest in phosphate rock, and the residual P2O5 content in phosphogypsum was as low as 0.36%. The morphology of the phosphogypsum crystal was uniform and coarse long strip. The main forms of residual impurities were silicate, aluminum fluoride with crystal water, aluminate, phosphate, and fluoride. Meanwhile, the residual amount of main impurities in phosphogypsum was significantly reduced. Through this novel method, the property of phosphogypsum can be improved through the generation process and is greatly beneficial for its utilization and the recycling development of the wet-process phosphoric acid industry.

Platinum nanoparticle-anchored metal-organic complex nanospheres by a coordination-crystallization approach for enhanced sonodynamic therapy of tumors.

The combination of noble metal nanoparticles with metal-organic complexes has attracted great attention for exploring new properties in biomedical application areas. So far, the preparation of noble metal nanoparticle-loaded metal-organic complexes often requires complex processes. Here, a simple coordination-crystallization approach was developed to prepare platinum nanoparticle-anchored metal-organic complexes (Pt-MOCs) by directly mixing disulfiram (DSF), chloroplatinic acid, and a reducing agent. The DSF and Pt ions first coordinate forming metal-organic complex nanospheres and then the Pt nanoparticles crystallized on the surface taking advantage of the coordination rate of the metal ions and organic ligand being greater than the reduction rate of the metal ions. The Pt-MOCs possess uniform and adjustable diameter (240-536 nm), and their surface potentials can also be modulated easily from -22 to +14 mV by adjusting the ratio of DSF and chloroplatinic acid. Phantom experiments show that the Pt-MOC nanospheres significantly improve the efficiency of singlet oxygen production after exposure to ultrasound irradiation. In vitro experiments show that the Pt-MOCs effectively produce reactive oxygen species and exhibit superior cytotoxicity for tumor cells under ultrasound irradiation compared to metal-organic complexes (MOCs) or Pt nanoparticles. Taken together, this work reports a coordination-crystallization approach to synthesize Pt-MOCs, which show excellent sonodynamic therapy for tumors.

Elasticity of mesoporous nanocapsules regulates cellular uptake, blood circulation, and intratumoral distribution.

The elasticity of nanoparticles plays a critical role in regulating nanoparticle-biosystem interactions. However, the elasticity of traditional organic-based carriers can only be regulated within a narrow range, and the effects of elasticity on in vivo biological processes have not been evaluated until now. Here, we construct hyaluronic acid modified mesoporous organosilica nanoparticles (MONs-HA) with a wide range of elasticity by an interior preferential etching approach and investigate the impact of their elasticity on in vitro cellular uptake, in vivo blood circulation, and tumor accumulation. The Young's moduli of the prepared MONs-HA are 1.64, 0.93, 0.78, 0.4 and 0.29 GPa (denoted as rigid MONs0-HA, semi-elastic MONs20-HA and MONs50-HA, elastic MONs100-HA and MONs200-HA), respectively. They all possess a similar hydrodynamic size (245-257 nm), similar surface electronegativity (-27 to -35 mV), and excellent dispersibility. In vitro experiments demonstrate that the elastic MONs100-HA and MONs200-HA (0.4 and 0.29 GPa) exhibit significantly greater cellular uptake relative to semi-elastic MONs20-HA and MONs50-HA (0.93 and 0.78 GPa) or rigid MONs0-HA (1.64 GPa). Simultaneously, these elastic MONs100-HA and MONs200-HA show an efficiently prolonged circulation time. In vivo results revealed that the elastic MONs100-HA show enhanced tumor accumulation compared to semi-elastic and rigid MONs-HA after intravenous administration. These desirable features of elasticity can direct the design of nanoplatforms, leading to an enhanced tumor delivery efficiency.

Endogenous/Exogenous Nanovaccines Synergistically Enhance Dendritic Cell-Mediated Tumor Immunotherapy.

Traditional dendritic cell (DC)-mediated immunotherapy is usually suppressed by weak immunogenicity in tumors and generally leads to unsatisfactory outcomes. Synergistic exogenous/endogenous immunogenic activation can provide an alternative strategy for evoking a robust immune response by promoting DC activation. Herein, Ti3 C2 MXene-based nanoplatforms (termed MXP) are prepared with high-efficiency near-infrared photothermal conversion and immunocompetent loading capacity to form endogenous/exogenous nanovaccines. Specifically, the immunogenic cell death of tumor cells induced by the photothermal effects of the MXP can generate endogenous danger signals and antigens release to boost vaccination for DC maturation and antigen cross-presentation. In addition, MXP can deliver model antigen ovalbumin (OVA) and agonists (CpG-ODN) as an exogenous nanovaccine (MXP@OC), which further enhances DC activation. Importantly, the synergistic strategy of photothermal therapy and DC-mediated immunotherapy by MXP significantly eradicates tumors and enhances adaptive immunity. Hence, the present work provides a two-pronged strategy for improving immunogenicity and killing tumor cells to achieve a favorable outcome in tumor patients.

Periodic mesoporous organosilica coupled with chlorin e6 and catalase for enhanced photodynamic therapy to treat triple-negative breast cancer.

Photodynamic therapy (PDT) has become a promising treatment option for highly aggressive triple-negative breast cancer (TNBC); however, hypoxia limits the efficacy of PDT and promotes tumour aggression. In this work, we first constructed a multifunctional yolk-shell structured nanoplatform consisting of periodic mesoporous organosilica (PMO) coupled with chlorin e6 (Ce6) and catalase (Catalase) (Yolk-Shell PMO-Ce6@Catalase) for enhanced PDT against TNBC. This nanoplatform has an organic-inorganic hybrid skeleton structure, a uniform size and good stability and biocompatibility. In vitro experiments showed that the nanoplatform has a good ability to generate singlet oxygen. Catalase can convert H2O2 into O2, increasing the concentration of oxygen around the cells and overcoming the problem of hypoxia in the tumour, which enhances the effects of PDT. The in vivo experimental results showed that PDT with the Yolk-Shell PMO-Ce6@Catalase nanoplatform, compared with free Ce6 and Yolk-Shell PMO-Ce6 PDT, can significantly inhibit tumour growth, revealing the most extensive cellular apoptosis and necrosis in the tumour area in this treatment group. Additionally, the histopathological results showed that PDT did not cause significant side effects to the major organs. Therefore, we believe that this Yolk-Shell PMO-Ce6@Catalase nanoplatform has excellent clinical potential for PDT against TNBC.

Disrupting stromal barriers to enhance photothermal-chemo therapy using a halofuginone-loaded Janus mesoporous nanoplatform.

Dense tumor stroma is the physiological barrier in drug delivery that prevents anticancer drugs from entering the tumor, thereby seriously limiting the drugs' therapeutic effect. In this study, a Janus nanoplatform consisting of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) and anti-stroma drug halofuginone (HF) (denoted as JPMO-Pt-HF), was developed to deplete the tumor stroma and synergistically treat breast cancer in BALB/c mice. The prepared JPMO-Pt had a uniform size of 245 nm, a good dispersion, an excellent in vitro and in vivo biocompatibility, and a high loading capacity for HF (up to 50 µg/mg). The antitumor experiments showed that the survival rate of 4 T1 cells exhibited an obvious downward trend when the cells were incubated with the JPMO-Pt-HF and irradiated with 808 nm laser. Moreover, the cell survival rate was only about 10% at 48 h when the HF concentration was 2.0 µg/mL. Notably, JPMO-Pt-HF under irradiation had an excellent synergistic therapeutic effect on tumor cells. In vivo antitumor experiment further showed that the JPMO-Pt-HF, in combination with laser irradiation, could minimize tumor growth, showing significantly better effects than those observed for the case of monotherapy involving photothermal therapy (PTT) (152 vs. 670 mm3, p < 0.0001) and HF (152 vs. 419 mm3, p = 0.0208). In addition, immunohistochemistry of tumor tissues indicated that JPMO-Pt-HF obviously reduced the relative collagen and α-smooth muscle actin (α-SMA) area fraction. Taken together, this research designs a new platform that not only possesses the ability to degrade the tumor matrix but also combines PTT and chemotherapeutic effects, and holds promise for effective tumor treatment.

Self-transformation synthesis of hierarchically porous benzene-bridged organosilica nanoparticles for efficient drug delivery.

Herein, a feasible outside-in hydrothermal self-transformation strategy is presented to fabricate hierarchically porous benzene-bridged organosilica nanoparticles (HPBONs), and detailed mechanistic investigations were performed to study the formation of hierarchically porous nanostructures. The obtained HPBONs consisted of a mesoporous core (2.3 nm) and a large mesoporous flocculent shell (12.6 nm), which corresponded to an overall diameter of âˆ¼ 200 nm and good water dispersibility, respectively. Owing to the unique hierarchically porous structure and high surface area (877 m2/g), HPBONs showed a high coloading capacity for the hydrophilic drug doxorubicin (DOX) and the hydrophobic photosensitizer chlorin e6 (Ce6) (355 µg/mg, 38 µg/mg, respectively) and acid-responsive DOX drug release (42.62%), leading to precise chemo-photodynamic therapy in vitro, as the cytotoxicity assay revealed 70% killing of breast cancer (MCF-7) cells. This research provides a new method to construct hierarchically porous organosilica-based nanodelivery systems.

Synthesis of Ethylenediaminetetraacetic Acid Disodium Salt Functionalized Magnetite/Chitosan Nanospheres for the Highly Efficient Removal of Methylene Blue.

In this paper, novel Ethylenediaminetetraacetic acid disodium salt (EDTA) functionalized magnetite/ chitosan nanospheres (Fe3O4/CS-EDTA) are synthesized by combining solvothermal method and chemical modification, and they are further applied as a kind of adsorbent to eliminate dye of methylene blue (MB) from wastewater. The properties as well as structure exhibited by the fabricated adsorbent are characterized through FTIR, XRD, TG and TEM, together with VSM. The impact exerted by sorption parameters (time of contact, initial dye concentration, temperature, etc.) on the adsorptions were evaluated in batch system. These results demonstrated that our magnetic materials held the adsorption capacity for MB of 256 mg g-1 (pH = 11), and the kinetic model of pseudo-second-order and the Langmuir model could make an effective simulation regarding the adsorption kinetics and isotherm, respectively. Besides, the external magnetic field can assist in easily separating dye adsorbed Fe3O4/CS-EDTA from solution for regeneration. The removal efficiency of recycled adsorbents remained above 92% in the 5th adsorption/desorption cycle. These superioritiesmake Fe3O4/CS-EDTA a high-efficientmultifunctional adsorbent for removing dyes from wastewater.

Intricately structured mesoporous organosilica nanoparticles: synthesis strategies and biomedical applications.

Intricately structured mesoporous organosilica nanoparticles (IMONs) are being increasingly studied from their synthesis strategies to their use in biomedical applications, because of their distinctive hierarchical structures, excellent physicochemical features and satisfactory biological properties. This minireview is the first to summarize recently developed IMONs, including yolk-shell-structured nanoparticles, multi-shelled hollow spheres, deformable nanocapsules, Janus nanostructures and virus-like bionic-structured nanocarriers, and describe the corresponding formation mechanisms and recent evolution of the strategies used to synthesize these kinds of IMONs. Structure-dependent biomedical applications, such as multidrug delivery, bioimaging, synergistic therapy and biocatalysis, are also discussed. Finally, we provide an outlook for IMONs ranging from their structural control to synthesis strategies and ending with their use in biomedical applications.

General Thermodynamic-Controlled Coating Method to Prepare Janus Mesoporous Nanomotors for Improving Tumor Penetration.

Artificial nanomotors are undergoing significant developments in several biomedical applications. However, current experimental strategies for producing nanomotors still have inherent drawbacks such as the requirement for expensive equipment, strict controlling of experimental conditions, and strenuous processes with several complex procedures. In this study, we describe for the first time a facile single-step thermodynamic-controlled coating method to prepare Janus mesoporous organosilica nanomotors. By controlling the total free energy of organosilica oligomers (G) from a low development level to a high level in the reaction system, the nonspontaneous nucleation on the platinum (Pt) nanosurface and the spontaneous nucleation in a solvent can be controlled, respectively. More importantly, we reveal that the molecular arrangement and contact angle of deposited organosilica on Pt cores vary with the total free energy of organosilica oligomers (G). Different values of θ would change the trend of detachment from Pt for organosilica nucleated cores and carry out diverse coating modes. These are indicated by the morphology evolution of platinum/organosilica hybrids, from naked platinum nanoparticles, evenly distributed organosilica shell/core, nonconcentric to typical Janus nanomotor. The prepared Janus mesoporous nanomotor (JMN) showed typical mesopore structures and active propelling behaviors under H2O2 stimulation. In addition, the JMN modified with hyaluronic acid exhibited excellent biocompatibility and improved tumor penetration under H2O2 stimulation. The successful construction of other nanomotor frameworks based on a gold-templated core proves the perfect applicability of the thermodynamic-coating method for the production of nanomotors. In conclusion, this work establishes a manufacturing methodology for nanomotors and drives nanomotors for promising biomedical applications.

General and facile syntheses of hybridized deformable hollow mesoporous organosilica nanocapsules for drug delivery.

Deformable materials have garnered widespread attention in biomedical applications. Herein, a controllable, general, and simple alkaline etching strategy was used to synthesize deformable hollow mesoporous organosilica nanocapsules (DMONs), in which multiple organic moieties were homogeneously incorporated into the framework. DMONs with double-, triple-, and even quadruple-hybridized frameworks were prepared by the selective introduction of organosilica precursors in accordance with the chemical homology principle through a surfactant-directed sol-gel procedure and a subsequent etching process in alkaline solution. The triple-hybridized DMONs possessed uniform and controllable diameters (100-330 nm), and large hollow cavities (50-270 nm). Liquid cell electron microscopy images demonstrated that the DMONs were deformable in solution. Elemental mapping images suggested that the organic components were homogeneous distribution within the entire DMONs framework. Statistical analysis of cell proliferation assays showed that breast cancer MCF-7 viability exceeded 85% when the cells are incubated with the triple-hybridized DMONs (800 µg mL-1) for 24 h. Histological assessments of main organs indicated no tissue injury or necrosis after intravenous injection of the DMONs 7 days (5 mg kg-1 body weight). Quantitative analysis indicated that the cellular uptake of the DMONs was 6-fold higher than that of their hard counterparts when the number of nanoparticles added was 1.25 × 104, and similar results were found for 4 T1 cells. Furthermore, doxorubicin (DOX) loaded triple-hybridized DMONs with a loading efficiency of 16.9 wt%, produced a strong killing effect on tumor cells. Overall, DMONs with various incorporated organic functional groups could serve as novel nanoplatforms for drug delivery in biomedical applications.

Magnetic mesoporous embolic microspheres in transcatheter arterial chemoembolization for liver cancer.

Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug loading, and imaging properties have not yet been constructed. Herein, we report a new magnetic mesoporous embolic microsphere that can simultaneously be loaded with doxorubicin (Dox), block vessels, and be observed by magnetic resonance imaging (MRI). The microspheres were prepared by decorating magnetic polystyrene/Fe3O4 particles with mesoporous organosilica microparticles (denoted as PS/Fe3O4@MONs). The PS/Fe3O4@MONs were uniformly spherical and large (50 µm), with a high specific surface area, uniform mesopores, and a Dox loading capacity of 460.8 µg mg-1. Dox-loaded PS/Fe3O4@MONs (PS/Fe3O4@MON@Dox) effectively inhibited liver cancer cell growth. A VX2 rabbit liver tumor model was constructed to study the efficacy of TACE with PS/Fe3O4@MON@Dox. In vivo, PS/Fe3O4@MON@Dox could be smoothly delivered through an arterial catheter to achieve chemoembolization. Moreover, PS/Fe3O4@MON@Dox and residual tumor parenchyma could be distinguished on MRI, which is of great significance for evaluating the efficacy of TACE. Histopathology showed that PS/Fe3O4@MON@Dox could be deposited in the tumor vessels, completely blocking the blood supply. Overall, PS/Fe3O4@MON@Dox showed good drug loading, embolization and imaging performance as well as potential for use in TACE. STATEMENT OF SIGNIFICANCE: Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug-loading, and imaging properties have not yet been constructed. In this work, we prepared magnetic mesoporous microspheres as a new embolic agent that can simultaneously load doxorubicin (Dox), block blood vessels and enable magnetic resonance imaging. Overall, this new embolic microsphere-mediated TACE strategy for liver cancer showed good therapeutic effects, and the PS/Fe3O4@MON@Dox embolic microspheres provide a new avenue for improving the efficacy of TACE for liver cancer and postoperative evaluation.

Periodic mesoporous organosilica-coated magnetite nanoparticles combined with lipiodol for transcatheter arterial chemoembolization to inhibit the progression of liver cancer.

Transcatheter arterial chemoembolization (TACE) is standard locoregional therapy for hepatocellular carcinoma (HCC) that involves the injection of chemotherapeutic drugs with embolic agents into tumor tissues through intra-arterial transcatheter infusion. TACE technology using lipiodol emulsion has been most widely used in the treatment of human HCC. However, lipiodol emulsions with anticancer drugs do not stably maintain high drug concentrations at tumor sites. Herein, we developed a dual-modality imaging nanoplatform for the TACE treatment of liver cancer by integrating periodic mesoporous organosilica (PMO) with magnetite (Fe3O4) nanoparticles and Cy5.5 molecules (denoted as Fe3O4@PMO-Cy5.5). Fe3O4@PMO-Cy5.5 showed an excellent doxorubicin (Dox)-loading capacity, sensitive drug release behavior under acidic conditions, and good biocompatibility. Moreover, Cy5.5-mediated optical imaging showed that Dox-loaded Fe3O4@PMO-Cy5.5 (Fe3O4@PMO-Cy5.5-Dox) could enter liver cancer cells and effectively inhibit their growth. In addition, Fe3O4@PMO-Cy5.5-Dox was used in combination with transarterial embolization for the treatment of in situ VX2 liver tumors in rabbits. Magnetic resonance imaging (MRI) evaluation showed that Fe3O4@PMO-Cy5.5-Dox perfused through arteries was deposited into liver tumors, and Fe3O4@PMO-Cy5.5-Dox combined with lipiodol to control liver tumors yielded the optimal therapeutic effect. In addition, histological analysis showed that compared with both lipiodol embolization and traditional lipiodol combined with Dox chemoembolization, Fe3O4@PMO-Cy5.5-Dox combined with lipiodol chemoembolization induced more complete tumor tissue necrosis. In summary, these results indicate that the Fe3O4@PMO-Cy5.5-Dox platform has the potential to become an advanced tool for the transarterial treatment of unresectable liver cancer.