Folate-Conjugated Fe₃O₄@SiO₂ Hollow Mesoporous Spheres for Targeted Anticancer Drug Delivery

Herein we developed a targeted anticancer drug delivery system based on folate-conjugated rattle-type Fe3O4@SiO2 hollow mesoporous spheres combining receptor-mediated targeting and magnetic targeting. Folic acid (FA) ligands were successfully grafted onto rattle-type Fe3O4@SiO2 hollow mesoporous spheres via amide reaction. The magnetization saturation value of folate-conjugated Fe3O4@SiO2 spheres (Fe3O4@SiO2−FA) was about 1.6 emu/g, and these spheres could be targeted under an external magnetic field. On the other hand, in vitro cytotoxicity and cell uptake of these Fe3O4@SiO2−FA spheres to Hela cells were evaluated. These Fe3O4@SiO2−FA spheres were nontoxic up to a concentration of 150 μg/mL, and further can be specifically taken up by Hela cells via FA receptor-mediated endocytosis. Doxorubicin hydrochloride (DOX), an anticancer drug, was introduced into Fe3O4@SiO2−FA spheres. The release of DOX from Fe3O4@SiO2−FA spheres had a sustained release pattern, and the DOX-loaded Fe3O4@SiO2−FA spheres exhibited greater cytotoxicity than free DOX and DOX-loaded Fe3O4@SiO2 spheres due to the increase of cell uptake of anticancer drug delivery vehicles mediated by the FA receptor. Therefore, we conclude that folate-conjugated Fe3O4@SiO2 hollow mesoporous spheres have potential for targeted anticancer drug delivery for cancer therapy

Hollow Mesoporous Silica/Poly(l-lysine) Particles for Codelivery of Drug and Gene with Enzyme-Triggered Release Property

We designed, for the first time, an enzyme-triggered drug and gene codelivery system combining hollow mesoporous silica (HMS) with enzyme degradable poly(l-lysine) (PLL) polymer to form HMS/PLL particles driven by electrostatic interaction between negatively charged gene and positively charged PLL polymer on the drug-loaded HMS particles. Fluorescein and cytosine–phosphodiester–guanine oligodeoxynucleotide (CpG ODN) were used as the model drug and gene, and the loading and the layer-by-layer assembly were evaluated by UV/vis analysis, zeta potential measurement, and gel electrophoresis. The fluorescein and CpG ODN loading capacities of the MFHMS/(CpG/PLL)3 particles were 28.8 and 97.1 μg/mg, respectively. Importantly, in vitro release results showed that the MFHMS/(CpG/PLL)3 particles exhibited an enzyme-triggered controlled release of fluorescein and CpG ODN simultaneously in the α-chymotrypsin solution, and the release rates of fluorescein and CpG ODN could also be controlled by changing the enzyme concentration. Therefore, this system has the advantages of both enzyme-triggered controlled release and codelivery of drug and gene and would have potential and promising applications in the field of biomedicine and cancer therapy

A Simple One-Pot Self-Assembly Route to Nanoporous and Monodispersed Fe₃O₄ Particles with Oriented Attachment Structure and Magnetic Property

Nanoporous and monodispersed Fe3O4 aggregated spheres with high surface area and oriented attachment structure have been successfully prepared by a polyol reduction process. The structure and morphology of the Fe3O4 particles were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and N2 adsorption−desorption technique. The spherical aggregates are formed by the assembling among the Fe3O4 primary nanoparticles (5 nm), and the average size of the spherical particles is around 100 nm. The nanopores are less than 3 nm in the aggregated spheres. Besides, the magnetic properties of these nanoporous particles are also investigated and the magnetization saturation value is about 42.8 emu/g

An Efficient Route to Rattle-Type Fe₃O₄@SiO₂ Hollow Mesoporous Spheres Using Colloidal Carbon Spheres Templates

Rattle-type Fe3O4@SiO2 hollow mesoporous spheres with large cavities have been successfully prepared by using the colloidal carbon spheres as the templates. The spheres are well monodisperse and nearly uniform in dimension with particle size of ca. 900 nm. The thickness of the mesoporous silica shell is about 100 nm, and only one Fe3O4 particle of ca. 100 nm in diameter is encapsulated in each hollow mesoporous silica sphere. The magnetic measurement indicated that the Fe3O4@SiO2 hollow mesoporous spheres exhibited ferromagnetic behavior with the magnetization saturation of 1.6 emu/g. Using aspirin as a model drug, the Fe3O4@SiO2 hollow mesoporous spheres showed high drug loading capacity and sustained release property. Therefore, this kind of magnetic hollow mesoporous spheres provides a very promising candidate for application in a targeted drug delivery system

Nanocasting Route to Ordered Mesoporous Carbon with FePt Nanoparticles and Its Phenol Adsorption Property

Magnetic ordered mesoporous carbon with superparamagnetic FePt nanoparticles has been successfully prepared via a simple nanocasting route. Polyfurfuryl alcohol was formed in the channels of mesoporous silica; FePt sources (iron(III) acetylacetonate (Fe(acac)3 and platinum(II) acetylacetonate (Pt(acac)2) were located in the framework of polyfurfuryl alcohol. After the carbonization process in argon, cubic FePt nanoparticles were formed in the carbon matrix. The FePt@C composites were characterized by X-ray diffraction, transmission electron microscopy, N2 adsorption−desorption technique, and SQUID magnetometer. The superparamagnetic FePt@C sample can be obtained at the lower FePt loading level; while at higher FePt loading levels, the FePt@C sample exhibits the ferromagnetic property. By use of phenol as a model pollutant, the adsorption capacities of FePt@C-L-700 and FePt@C-H-700 can reach 139 and 114 mg/g, respectively. The magnetic separation can also be realized using an external magnetic field. Therefore, the magnetic ordered mesoporous carbon composite has potential application as a catalyst support and adsorbent

Mesoporous Silica Nanoparticles Capped with Graphene Quantum Dots for Potential Chemo–Photothermal Synergistic Cancer Therapy

In this study, mesoporous silica nanoparticles (MSNs) have been successfully capped with graphene quantum dots (GQDs) to form multifunctional GQD–MSNs with the potential for synergistic chemo–photothermal therapy. The structure, drug-release behavior, photothermal effect, and synergistic therapeutic efficiency of GQD–MSNs to 4T1 breast cancer cells were investigated. The results showed that GQD–MSNs were monodisperse and had a particle size of 50–60 nm. Using doxorubicin hydrochloride (DOX) as a model drug, the DOX-loaded GQD–MSNs (DOX–GQD–MSNs) not only exhibited pH- and temperature-responsive drug-release behavior, but using near-infrared irradiation, they efficiently generated heat to kill cancer cells. Furthermore, GQD–MSNs were biocompatible and were internalized by 4T1 cells. Compared with chemotherapy and photothermal therapy alone, DOX–GQD–MSNs were much more effective in killing the 4T1 cells owing to a synergistic chemo–photothermal effect. Therefore, GQD–MSNs may have promising applications in cancer therapy

Mesoporous Bioactive Glass–Graphene Oxide Composite Aerogel with Effective Hemostatic and Antibacterial Activities

Hemorrhage and infection after emergency trauma are two main factors that cause deaths. It is of great importance to instantly stop bleeding and proceed with antibacterial treatment for saving lives. However, there is still a huge need and challenge to develop materials with functions of both rapid hemostasis and effective antibacterial therapy. Herein, we propose the fabrication of a composite aerogel mainly consisting of mesoporous bioactive glass (MBG) and graphene oxide (GO) through freeze-drying. This composite aerogel has a three-dimensional porous structure, high absorption, good hydrophilicity, and negative zeta potential. Moreover, it exhibits satisfactory hemostatic activities including low BCI, good hemocompatibility, and activation of intrinsic pathways. When applied to rat liver injury bleeding, it can decrease 60% hemostasis time and 75% blood loss amount compared to medical gauze. On the other hand, the composite aerogel shows excellent photothermal antibacterial capacity against Staphylococcus aureus and Escherichia coli. Animal experiments further verify that this composite aerogel can effectively kill bacteria in wound sites via photothermal treatment and promote wound healing. Hence, this MBG–GO composite aerogel makes a great choice for the therapy of emergency trauma with massive hemorrhage and bacterial infection

Mesoporous Silica Nanoparticles/Hydroxyapatite Composite Coated Implants to Locally Inhibit Osteoclastic Activity

In an attempt to improve implant-bone integration and accelerate bone fracture healing from resisting osteoclastic resorption point of view, we have employed a novel procedure to develop a mesoporous silica nanoparticles/hydroxyapatite (MSNs/HA) composite coating onto stainless Kirschner wire substrate. Characterizations of the surface microstructures indicated enlarged specific surface area compared to HA-coated wires as control, thus the MSNs/HA composite coated implants are endowed with abilities to locally deliver biomedical substances and enhance fracture healing. Herein, zoledronic acid (ZOL) as a model drug, different doses of which were immobilized in the mesoporous coating toward decreasing osteoclastic resorption activity. The loading capacities of ZOL increased almost eight-folds to that of pure HA coating, and the introduction of MSNs obviously retarded ZOL release to achieve a more sustained release profile. After certain periods of osteoclast like cells co-culturing with ZOL contained wires, tartrat-resistant acid phosphatases (TRAP) staining of polynucleated cells and a pit formation assay were performed to investigate the ZOL dose-dependent anti-resorption activity. The promoted local effect on osteoclasts will be of clinical benefit to support implant integration and bone repair

Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy

Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient <i>in vivo</i> magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (<i>r</i>₁ = 9.43 mM^–1 s^–2) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death <i>in vitro</i> and suppressing the tumor growth <i>in vivo</i>. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed high-performance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine

Image1_Rhynchophylline Regulates Calcium Homeostasis by Antagonizing Ryanodine Receptor 2 Phosphorylation to Improve Diabetic Cardiomyopathy.TIF

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to heart failure and death, for which there is no effective treatment. Rhynchophylline (Rhy) is the main effective component of the Chinese herbal medicine Uncaria rhynchophylla, which mainly acts on the cardiovascular and nervous systems. However, its role in protecting against DCM remains unexplored. The present study sought to reveal the mechanism of Rhy in improving type 2 diabetes mellitus (T2DM) myocardial lesions from the perspective of regulating calcium homeostasis in cardiomyocytes. We prepared a mouse model of T2DM using a high-fat diet combined with low doses of streptozotocin. The T2DM mice were given 40 mg/kg of Rhy for 8 weeks. The results showed that Rhy can attenuate cardiac pathological changes, slow down the heart rate, decrease serum cardiac enzyme levels, reduce cardiomyocyte apoptosis, enhance cardiomyocyte contractility, and raise the calcium transient amplitude in T2DM mice. Further, Rhy downregulated the phosphorylation level of ryanodine receptor 2, upregulated the phosphorylation level of phospholamban, protected mitochondrial structure and function, and increased adenosine triphosphate levels in the cardiac tissue of T2DM mice. Our results demonstrated that Rhy may protect against myocardial damage in T2DM mice and promote cardiomyocyte contraction, and its mechanism of action seems to be related to the regulation of intracellular calcium homeostasis.</p