Meng Dang

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.

Hollow periodic mesoporous organosilica nanospheres by a facile emulsion approach.

Periodic mesoporous organosilicas (PMOs) with homogeneously incorporated organic groups, highly ordered mesopores, and controllable morphology have attracted increasing attention. In this work, one-step emulsion approach for preparation of hollow periodic mesoporous organosilica (HPMO) nanospheres has been established. The method is intrinsically simple and does not require any sacrificial templates, corrosive and toxic etching agents. The obtained HPMO nanospheres have high surface area (∼950m(2)g(-1)), accessible ordered mesochannels (∼3.4nm), large pore volume (∼3.96cm(3)g(-1)), high condensation degree (77%), and diameter (∼560nm), hollow chamber size (∼400nm), and shell thickness (∼80nm). Furthermore, cytotoxicity show the cell viability is higher than 86% after incubating with the HPMO nanospheres at a concentration of up to 1200μgmL(-1) for 24h. The hemolysis of HPMO nanospheres is lower than 1.1% at concentrations ranging from 10 to 2000μgmL(-1). The lower hemolysis and cytotoxicity make the HPMO nanospheres great promise for future biomedical applications.

Synthesis of sandwich-like molybdenum sulfide/mesoporous organosilica nanosheets for photo-thermal conversion and stimuli-responsive drug release

Sandwich-like molybdenum sulfide/mesoporous organosilica nanosheets (denoted as MoS2@MOS) have been prepared for the first time via direct growth of ethane-bridged mesostructured organosilica on MoS2 nanosheets by using cetyltrimethylammonium bromide (CTAB) as structure directing agent. The obtained MoS2@MOS nanosheets possess well-defined sandwich-like structure, high surface area (∼920cm2/g), uniform pore size (∼4.2nm), large pore volume (∼1.41cm3g-1). In vitro cytotoxicity assessments demonstrate that the MoS2@MOS nanosheets have excellent biocompatibility. Owing to the encapsulation of the MoS2, the obtained MoS2@MOS nanosheets have photo-thermal conversion capability and photo-thermally controlled drug release property. These properties make the MoS2@MOS nanosheets promising for biomedical applications.

Small size mesoporous organosilica nanorods with different aspect ratios: Synthesis and cellular uptake

In the work, small size thioether-bridged mesoporous organosilica nanorod (MONRs) are successfully synthesized using cetyltrimethylammonium bromide (CTAB) as structure-directing agent and bis[3-(triethoxysilyl)propyl]tetrasulfide (TETS) and tetraethoxysilane (TEOS) as co-precursors. The MONRs have tunable aspect ratios of 2, 3, and 4 (denoted as MONRs-2, MONRs-3, and MONRs-4), small and controllable lengths (75-310nm), high surface area (570-870cm2g-1), uniform mesopores (2.4-2.6nm), large pore volume (0.34cm3g-1), and excellent biocompatibility. The uptake of the MONRs by multidrug resistant human breast cancer MDR-MCF-7 cells is related to their aspect ratios. The MONRs-3 shows a faster and higher cellular internalization compared to the MONRs-4 and MONRs-2, respectively. Thanks to the high cellular uptake, doxorubicin (DOX) loaded MONRs-3 show obviously improved chemotherapeutic effect on MDR-MCF-7 cancer cells. It is expected that the MONRs provide a useful platform for drug delivery and therapeutics.

Mesoporous organosilica nanoparticles with large radial pores via an assembly-reconstruction process in bi-phase

Mesoporous organosilica nanoparticles (MONs) have attracted increasing interest for guest molecule delivery. In this work, we prepared MONs with radially oriented large pores for the first time in a water-ethanol/n-hexane biphasic reaction system. The MONs possess ethane-incorporated organosilica frameworks, large radial pores with openings of 17-78 nm, a high surface area (1219 cm2 g-1), a large pore volume (2.2 cm3 g-1), tunable diameters (124-287 nm), and excellent biocompatibility. We reveal that the formation of large pore MONs in the biphasic reaction system undergoes a surfactant-directed self-assembly following mesostructure reconstruction, providing a new mechanism for the preparation of large mesoporous nanoparticles. Also, the effects of the reaction parameters including temperature and the stirring rate on the pore size are systemically investigated. Furthermore, large pore MONs were loaded with bovine serum albumin (BSA) and small interference RNA (siRNA), which exhibit high protein loading and siRNA delivery capabilities, suggesting the potential of the MONs for biomedical applications.

Tumor Acidic Microenvironment Targeted Drug Delivery Based on pHLIP-Modified Mesoporous Organosilica Nanoparticles

Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we first construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility, and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment. Moreover, the engineered MONs exhibit higher cellular uptake in pH 6.5 medium by MDA-MB-231 and MCF-7 cells than the particles decorated with polyethylene glycol (PEG). Importantly, the pHLIP-mosaic MONs with DOX displays better cytotoxic effects against the breast cancer cells in pH 6.5 medium than pH 7.4 medium. The in vivo experiments demonstrate that the pHLIP modified MONs are accumulated in the orthotopic breast cancer via targeting to acidic tumor microenvironment while no serious pathogenic effects was observed. After loading DOX, the pHLIP-modified MONs display better therapeutic effects than the control groups on the growth of MCF-7 breast cancers, showing promise for enhancing chemotherapy.

Facile synthesis of yolk–shell structured monodisperse mesoporous organosilica nanoparticles by a mild alkalescent etching approach

In the work, yolk-shell structured mesoporous organosilica nanoparticles (YSMONs) are successfully prepared by a mild alkalescent etching approach. The method is very convenient, in which mesostructured organosilica nanospheres are directly transformed into yolk-shell structures after etching with mild alkalescent solution (e.g. sodium carbonate solution). The prepared YSMONs have ethane-bridged frameworks, a monodisperse diameter (320 nm), a large pore volume (1.0 cm3 g-1), a uniform mesopore (2.4 nm) and a high surface area (1327 m2 g-1). In vitro cytotoxicity and hemolysis assays demonstrate the ethane-bridged YSMONs possess excellent biocompatibility and low hemolysis activity. In addition, the YSMONs show a high loading capacity up to 181 μg mg-1 for anti-cancer drug doxorubicin (DOX). Confocal laser scanning microscopy and flow cytometry analyses show that the DOX loaded YSMONs (YSMONs-DOX) can be effiectively internalized by multidurg resistant MCF-7/MDR human breast cancer cells. The chemotherapy against MCF-7/MDR cells demonstrate that the YSMONs-DOX possess higher therapeutic efficacy compared to that of free DOX, suggesting that the YSMONs synthesized by the mild alkalescent etching method have great promise as advanced nanoplatforms for biological applications.

Biphasic-to-monophasic successive Co-assembly approach to yolk–shell structured mesoporous organosilica nanoparticles

In this work, we report a facile biphasic-to-monophasic successive co-assembly approach to synthesize yolk-shell structured mesoporous organosilica nanoparticles (MONs). The yolk-shell structured MONs possess ethane-bridged frameworks, high surface area (1023m2g-1), radially oriented mesochannels (3.8nm), large pore volume (0.99cm3g-1), and tunable diameter (147-324nm) and shell thickness (23-53nm). The biphasic-to-monophasic successive co-assembly method is intrinsically simple and requires neither sacrificial templates nor multistep coating processes. The key of the method is that the interiors of the mesostructured organosilica nanospheres grown in the biphasic system have a lower condensation degree and Si-C-C-Si species content than the outer shells formed in the monophasic system. Thus, the interior layer is attracted by OH-1 anions and dissolved in the monophasic system, forming the yolk-shell structures. In vitro cytotoxicity and haemolysis assays demonstrate that the ethane-bridged yolk-shell MONs possess excellent biocompatibility. Furthermore, the chemotherapy drug doxorubicin (DOX) is loaded into the yolk-shell MONs to kill drug-resistant MCF-7/ADR human breast cancer cells. Compared with free DOX and DOX-loaded typical MONs, the DOX-loaded yolk-shell MONs have higher chemotherapeutic efficacy against MCF-7/ADR cells, suggesting the great potential of yolk-shell MONs synthesized via the biphasic-to-monophasic successive co-assembly approach in the biomedical field.