Extracellular Vesicle-Inspired Minimalist Flexible Nanocapsules Assembled with Whole Active Ingredients for Highly Efficient Enhancement of DC-Mediated Tumor Immunotherapy.

The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8+ and CD4+ T cells targeting specific antigens, reducing immunosuppression by regulatory T cells, and boosting the populations of effector memory T cells. These findings underscore that the simple yet potent strategy of employing minimal flexible nanocapsules markedly enhances DC-mediated antitumor immunotherapy, offering promising avenues for future clinical 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.

Peptide amphiphile inspired self-assembled, ordered gold nanocomposites for improved sensitivity of electrochemical immunosensor: Applications in determining the total aflatoxin amount in food stuffs.

In peptide amphiphile, The positively charged amino acid arginine can inspire the ordered self-assembly of gold nanocomposites (AuNPs), transfer positive charge to AuNPs, and weaken the aggregation of AuNPs by electrostatic repulsion, whereas hydrophobic fatty acid chains regulate the self-assembly of AuNPs through hydrophobic interaction, which may be a novel strategy to overcome disordered arrangement and aggregation of AuNPs to obtain an ultra-sensitive electrochemical immunosensor for determining the total aflatoxin amount. In this study, a peptide amphiphile (C14R5), composed of five arginine residues as the hydrophilic chain and myristic acid as the hydrophobic chain, inspired AuNPs to form monodispersed hollow raspberry-like AuNPs (rasAuNPs). rasAuNPs could captured and immobilized large amounts of aflatoxin antigens via the Au-S bonds, resulting in binding to more anti-aflatoxin antibodies. In the absence of aflatoxins, the enriched antigens bound to abundant antibodies, resulting in a low blank signal current. By contrast, in the presence of aflatoxins, enough antibodies could bind to the targets and less antibodies could recognize the antigens, increasing the detection signal intensity. Under the optimal conditions, the developed sensor demonstrated a wide linear range (0.13-29.06 pg mL-1) and a low limit of detection for total aflatoxins (0.05 pg mL-1) using a mixed standard (AFB1: AFB2: AFG1: AFG2 with a weight ratio of 1:1:1:1) in peanut, peanut milk, and maize powder samples. Hence, this novel strategy improves the sensitivity of electrochemical sensors and can be easily applied to detect other small molecule compound for the purpose of food safety.

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.

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.

Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability.

Photodynamic therapy (PDT) has been widely used in cancer treatment. However, hypoxia in most solid tumors seriously restricts the efficacy of PDT. To improve the hypoxic microenvironment, we designed a novel mesoporous platinum (mPt) nanoplatform to catalyze hydrogen peroxide (H2O2) within the tumor cells in situ without an extra enzyme. During the fabrication, the carboxy terminus of the photosensitizer chlorin e6 (Ce6) was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol (SH-PEG-NH2) by a condensation reaction, and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2. Material, cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2O2 to produce oxygen (O2) and that Ce6 transformed O2 to generate reactive oxygen species (ROS) upon laser irradiation. The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation. Due to the high atomic number and good near-infrared absorption for Pt, this Pt@PEG-Ce6 nanoplatform showed computed tomography (CT) and photoacoustic (PA) dual-mode imaging ability, thus providing an important tool for monitoring the tumor hypoxic microenvironment. Moreover, the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-1α (HIF-1α) and programmed death-1 (PD-1) in tumors, discussing the relationship between hypoxia, PD-1, and PDT for the first time.

Mesoporous platinum nanoparticle-based nanoplatforms for combined chemo-photothermal breast cancer therapy.

High-efficiency cancer treatment remains the main challenge at present. In this study, a mesoporous platinum nanoparticle- (mesoPt) based nanoplatform is exported for effective tumor treatment, integrating computed tomography (CT) imaging, photothermal conversion, and chemotherapeutic drug delivery capabilities. Mesoporous platinum nanoparticles are facilely synthesized by using Pluronic F127 as a structure-directing agent without seeds or organic reagents and have a spherical structure and uniform diameter of 94 nm. The surface of the mesoPt is modified with polyethylene glycol (PEG), and the prepared mesoPt-PEG shows excellent biocompatibility. Doxorubicin (Dox)-loaded PEG@Pt (PEG@Pt/Dox) is further prepared by electrostatic adsorption and the drug-loading capacity is as high as 25%. In vitro studies demonstrate that Dox can be controllably released from PEG@Pt/Dox in pH 5.5 phosphate buffered solution (PBS). Confocal imaging verifies that PEG@Pt/Dox can efficiently enter Dox-resistant breast cancer cells (MCF-7/ADR), deliver Dox into the cytoplasm when incubated for 1 h or 12 h, and release Dox into the nucleus when incubation is prolonged to 24 h. Cell transmission electron microscopy and flow cytometry also confirm that PEG@Pt/Dox could be internalized by cells. Upon irradiation by an 808 nm laser, the anticancer effect of PEG@Pt/Dox is significantly improved and kills approximately 84% of cancer cells when the concentration of Dox is 8 µg/mL. The killing efficacy of MCF-7/ADR cells is significantly higher in the combination group than in the monochemotherapy group. Hence, multifunctional nanoplatform PEG@Pt/Dox presents an effective strategy to realize efficient combination of chemotherapy and photothermals for drug-resistant cancer.

Simultaneous T Cell Activation and Macrophage Polarization to Promote Potent Tumor Suppression by Iron Oxide-Embedded Large-Pore Mesoporous Organosilica Core-Shell Nanospheres.

Nanomaterial-based immunotherapy stimulating T cell activation or tumor-associated macrophage (TAM) conversion holds great promise for promoting tumor suppression. Herein, a novel nanoplatform, iron oxide-embedded large-pore mesoporous organosilica nanospheres (IO-LPMONs), is prepared for the first time to simultaneously activate cytotoxic T cells and polarize macrophages for potent tumor immunotherapy. The IO-LPMONs have large mesopores (6.3 nm) and inorganic-organic hybrid shells, which contribute to a high payload (500 µg mg-1 ) of the antigen ovalbumin (OVA). The IO-LPMONs effectively deliver OVA to dendritic cells (DCs) and activate DCs. Subsequently, high activation of both CD4+ and CD8+ effector antigen-specific T cells is achieved for powerful antitumor effects. Moreover, the IO-LPMONs also act as an immune modulator to polarize TAMs from an immunosuppressive M2 to a tumor-killing M1 phenotype, which induces efficient apoptosis of tumor cells. The combined T cell activation and macrophage polarization strategy based on the IO-LPMONs elicits remarkable combined antitumor effects in vivo, showing great promise for tumor treatment.

Facile preparation of near-infrared fluorescence and magnetic resonance dual-modality imaging probes based on mesoporous organosilica nanoparticles.

In this work, near-infrared fluorescence (NIRF) and magnetic resonance (MR) dual-modality imaging probes are prepared by conjugating maleimide derivative cyanine dye (Mal-Cy5.5), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), and RGD peptide (Mal-PEG2-RGD) on thioether-bridged mesoporous organosilica nanoparticles (MONs) via click reaction. Fourier transform infrared (FT-IR) spectra, zeta potentials, UV-vis spectra, and energy dispersive X-ray (EDX) spectrum confirm the successful modifications of the functional molecules on the MONs. The prepared MON-Gd-Cy5.5-RGD probes shows excellent NIRF and MR imaging properties, and the relaxivity rate (r1) is measured up to 2.85 mM-1 s -1. In addition, the MON-Gd-Cy5.5-RGD probes show excellent in vitro and in vivo biocompatibility. Confocal laser scanning microscopy and flow cytometry demonstrate that the MON-Gd-Cy5.5-RGD can efficiently target to MDA-MB-231 tumor cells. Additionally, ex vivo NIFR and in vivo MR imaging demonstrate that the MON-Gd-Cy5.5-RGD probes can accumulate in tumor and improve the signals of tumor.

Intercellular adhesion molecule 1 antibody-mediated mesoporous drug delivery system for targeted treatment of triple-negative breast cancer.

The development of effective targeted therapies for triple negative breast cancer (TNBC) remains a challenge. This targeted drug delivery system used a near-infrared fluorescence dye cyanine 5.5 (Cy5.5) and an ICAM-1 antibody on thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The ICAM-1 antibody and cyanine 5.5-engineered PMOs (PMO-Cy5.5-ICAM) offer excellent in vivo and in vitro biocompatibility. The PMO-Cy5.5-ICAM shows a loading capacity up to 400 mg/g of doxorubicin (DOX). The drug release profile of the DOX-loaded targeted delivery system (DOX@PMO-Cy5.5-ICAM) is pH-sensitive. Confocal microscopy showed that the PMO-Cy5.5-ICAM efficiently targets and enters TNBC cells. In in vivo experiments, the DOX@PMO-Cy5.5-ICAM accumulates more in TNBCs than in the control groups and exhibits better therapeutic effects on TNBC; thus, it is a promising treatment strategy for TNBC.

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.

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.

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.

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.

Capillary electrochromatography immunoassay for alpha-fetoprotein based on poly(guanidinium ionic liquid) monolithic material.

Alpha-fetoprotein (AFP) is widely used as a tumor marker for the serum diagnosis of primary hepatoma. Sensitive detection of AFP level plays an important role in the early diagnosis of disease and highly reliable prediction. In this study, a novel non-competitive immunoassay (IA) based on poly(guanidinium ionic liquid) monolithic material was developed for detecting ultra trace levels of AFP in capillary electrochromatography (CEC) mode. The AFP was mixed with an excess amount of fluorescently labeled antibody. After incubation, the immunocomplex was separated from the free labeled antibody and detected by CEC coupled with laser-induced fluorescence detector. Under the optimized conditions, the developed CEC-IA performed a low detection limit of 0.05 µg L-1 (S/N = 3) and a wide linearity ranging from 0.1 to 1000 µg L-1 for AFP, which can be largely attributed to the high separation and enrichment efficiency of poly(guanidinium ionic liquid) monolithic material for the targets. The application of this method was demonstrated by determining AFP in human serum.

Periodic Mesoporous Organosilica Coated Prussian Blue for MR/PA Dual-Modal Imaging-Guided Photothermal-Chemotherapy of Triple Negative Breast Cancer.

Complete eradication of highly aggressive triple negative breast cancer (TNBC) remains a notable challenge today. In this work, an imaging-guided photothermal-chemotherapy strategy for TNBC is developed for the first time based on a periodic mesoporous organosilica (PMO) coated Prussian blue (PB@PMO) nanoplatform. The PB@PMOs have organic-inorganic hybrid frameworks, uniform diameter (125 nm), high surface area (866 m2 g-1), large pore size (3.2 nm), excellent photothermal conversion capability, high drug loading capacity (260 µg mg-1), and magnetic resonance (MR) and photoacoustic (PA) imaging abilities. The MR and PA properties of the PB@PMOs are helpful for imaging the tumor and showing the accumulation of the nanoplatform in the tumor region. The bioluminescence intensity and tumor volume of the MDA-MB-231-Luc tumor-bearing mouse model demonstrate that TNBC can be effectively inhibited by the combined photothermal-chemotherapy than monotherapy strategy. Histopathological analysis further reveals that the combination therapy results in most extensive apoptotic and necrotic cells in the tumor without inducing obvious side effect to major organs.

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.

Gold nanorod embedded large-pore mesoporous organosilica nanospheres for gene and photothermal cooperative therapy of triple negative breast cancer.

To date, clinicians still lack an effective strategy to treat triple negative breast cancer (TNBC). In this work, we design for the first time a gold nanorod embedded large-pore mesoporous organosilica (GNR@LPMO) nanoplatform for gene and photothermal cooperative therapy of TNBC. The synthesized GNR@LPMOs possess a uniform size (175 nm), high surface area (631 m2 g-1), large pore size, excellent photothermal efficiency, and good biocompatibility. Thanks to the large-pore mesoporous organosilica layer, the GNR@LPMO nanoplatforms display much higher loading capacity of siRNA compared with traditional liposome and bare gold nanorods. Thus, functional siRNA can be efficiently delivered into TNBC cells by GNR@LPMOs, causing much higher cell apoptosis through knocking down the PLK1 proteins. By combining the effective gene delivery and photothermal abilities, the GNR@LPMO nanoplatforms are further used for gene and photothermal cooperative therapy of TNBC, which induce a 15 fold higher mice tumor inhibition rate than sole therapy modality, indicating the potential clinical use of this novel nanoplatform in treating TNBC.

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway.

Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue.

Gene expression profile in the early stage of angiotensin II-induced cardiac remodeling: a time series microarray study in a mouse model.

BACKGROUND/AIMS: Angiotensin II (Ang II) plays a critical role in the cardiac remodeling contributing to heart failure. However, the gene expression profiles induced by Ang II in the early stage of cardiac remodeling remain unknown. METHODS: Wild-type male mice (C57BL/6 background, 10-weeek-old) were infused with Ang II (1500 ng/kg/min) for 7 days. Blood pressure was measured. Cardiac function and remodeling were examined by echocardiography, H&E and Masson staining. The time series microarrays were then conducted to detected gene expression profiles. RESULTS: Microarray results identified that 1,489 genes were differentially expressed in the hearts at day 1, 3 and 7 of Ang II injection. These genes were further classified into 26 profiles by hierarchical cluster analysis. Of them, 4 profiles were significant (No. 19, 8, 21 and 22) and contained 904 genes. Gene Ontology showed that these genes mainly participate in metabolic process, oxidation-reduction process, extracellular matrix organization, apoptotic process, immune response, and others. Significant pathways included focal adhesion, ECM-receptor interaction, cytokine-cytokine receptor interaction, MAPK and insulin signaling pathways, which were known to play important roles in Ang II-induced cardiac remodeling. Moreover, gene co-expression networks analysis suggested that serine/cysteine peptidase inhibitor, member 1 (Serpine1, also known as PAI-1) localized in the core of the network. CONCLUSIONS: Our results indicate that many genes are mainly involved in metabolism, inflammation, cardiac fibrosis and hypertrophy. Serpine1 may play a central role in the development of Ang II-induced cardiac remodeling at the early stage.