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With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.

According to our previous experiment, graphene quantum dots capped in hollow mesoporous silica nanoparticles, denoted as GQDs@hMSN, and its conjugates exhibited great potential for medical applications due to their commendable biocompatibility. Due to the fluorescence and structural stability, and enormous porosity, polyethylene glycol (PEG) modified GQDs@hMSN (GQDs@hMSN-PEG) is a good candidate in a drug carrying and delivery system. However, the goal of targeted drug delivery couldn't be achieved simply by utilizing the enhanced permeability and retention (EPR) effect of tumors. In this study, GQDs@hMSN-PEG was further functionalized with vascular endothelial growth factor antibodies (VEGF Abs) for VEGF targeting of breast tumors. Doxorubicin (DOX) was loaded into GQDs@hMSN-VEGF Abs with a drug loading capacity of 0.80 mg DOX per mg GQDs@hMSN. With GQDs as the fluorescent source, GQDs@hMSN-VEGF Abs demonstrated strong fluorescence intensity in VEGF-positive cells. Results from in vitro and in vivo targeting experiments indicated that GQDs@hMSN-VEGF Abs had high specificity on tumor vasculature, and it could be used as an image-guidable, tumor-selective delivery nanoplatform for breast cancer.

Low eutectic of lauric acid and stearic acid is one of drug loading candidates for its phase transformation at a certain temperature. Herein we demonstrated a combined photothermal-chemotherapy for breast cancer with near-infrared (NIR) triggered phase transition materials (PCM), which was conjugated with polydopamine (PDA) as the photosensitive agent. The PCM nanoparticles had diameters of ~75 nm based on scanning electron microscope (SEM) and dynamic laser scattering (DLS) measurement. Systematic in vitro and in vivo studies have been performed to investigate the stability, biosafety, photothermal performance, and drug delivery and release of PCM conjugates. Temperature measurement confirmed the prepared PDA modified material still showed strong photothermal effect after five cycles, which was higher than that of IR780 conjugated ones. In vivo photothermal imaging showed that the temperature of the tumor site reached 50.8 °C after 3 h of intravenous injection of PCM conjugates. More effective therapy of near-infrared (NIR)-assisted PDA-M@PCM in 4T1 bearing mice was witnessed when compared with that of non-NIR-assisted ones. Enhanced therapy in 4T1 tumor was demonstrated in DOX-loaded PDA-M@PCM by fluorescence imaging. This NIR-triggered PCM based nanoplatform can serve as useful tool for light-assisted combined tumor therapy.

Common bacterial pathogens have become resistant to traditional antibiotics, representing an indispensable public health crisis. Photodynamic therapy (PDT), especially when common visible light sources are used as photodynamic power, is a promising bactericidal method. Based on the special photodynamic properties triggered by commonly available light emitting diode (LED) lamps, a kind of graphene quantum dots (GQDs) based composite system (termed GQDs@hMSN(EM)) was prepared through loading both GQDs and erythromycin (EM) into the hollow mesoporous silica nanoparticle (hMSN), aiming to achieve joint antimicrobial effect. Bacterial density experiments confirmed that GQDs@hMSN(EM) had combined antimicrobial effects from photodynamic effect and drug release on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In animal models, the healing degree of wounds infected by bacteria also confirmed that GQDs@hMSN(EM) group had the best therapeutic effect, with the significantly reduced inflammatory factors in blood. Different from traditional GQDs synthesized by solvothermal method, the as-prepared GQDs@hMSN can produce singlet oxygen (1O2) under light exposure to destroy the structure of bacteria, thus achieving highly efficient antimicrobial effect. The GQDs@hMSN(EM) in this work possesses good antimicrobial activity, sufficient drug loading, and controllable drug release ability, which provides a new opportunity for GQDs-based nanoplatform to enhance antimicrobial effect and reduce their drug resistance.

Silane coupling agent is applied to modify polypropylene fiber. The modification effectively transfers the hydrophobic surface of polypropylene fiber to hydrophilic surface. Results from FT-IR, SEM and contact angle meter suggest that that the surface functional groups, the morphology and hydrophilia of polypropylene fiber is changed during the hydrolysis reactions of silane coupling agent. The modification process not only improve the surface hydrophilia of polypropylene fiber, but also convert the smooth surface of unmodified fibers to rough surface of modified fibers which gives stronger interface bonding force between fiber and substrate in the field of composite applications.

Graphene quantum dots capped in hollow mesoporous silica nanoparticles (GQDs@hMSN) exhibited great potential in medical applications due to its good optical properties and high drug loading capacity. Compared with antibodies, peptide has a better affinity with target proteins. Herein, we demonstrated efficient targeting of triple-negative breast cancer with GQDs@hMSN, which was conjugated to a peptide ligand, F3 against nucleolin, to form GQDs@hMSN-F3. The core/shell GQDs@hMSN and GQDs@hMSN-F3 had diameters of 100 nm and 130 nm, respectively, based on transmission electron microscope (TEM) and dynamic laser scattering (DLS) measurement. Doxorubicin (DOX) was loaded onto GQDs@hMSN with a relatively high loading capacity. Systematic in vitro and in vivo studies were performed to investigate the targeting specificity and tissue distribution of GQDs@hMSN conjugates. Fluorescence microscopy examination and flow cytometry confirmed the targeting specificity of F3-attached GQDs@hMSN conjugates against cell nucleolin. A more potent uptake of GQDs@hMSN-F3 in MDA-MB-231 nodules was witnessed when compared with that of non-targeted GQDs@hMSN. Based on the findings from cellular targeting and in vivo fluorescence imaging, F3-attached GQDs@hMSN conjugates had the potential to serve as an image-guidable, tumor-selective cargo delivery nanoplatform.

Due to the excellent photoluminescent properties and singlet oxygen (1O2) generating efficiency, graphene quantum dots (GQDs) with maximal emission in near-infrared region (NIR) exhibited great potential in cancer imaging and therapy. However, GQDs can be cleared quickly via the renal system in vivo because of their ultrasmall size, which leads to the compromised cancer cell killing efficacy. Here, we report a hybrid nanoplatform, where GQDs were incorporated into the cavity of hollow mesoporous silica nanoparticles (hMSN) to form GQDs@hMSN-PEG nanoparticles (NPs). Optical characterization indicated that GQDs@hMSN-PEG NPs still maintained good absorption and emission properties from GQDs, and the composite NPs still possessed similar 1O2 generating efficiency. GQDs@hMSN-PEG NPs exhibited good biocompatibility in vitro and in vivo. High cargo-loading efficiency was achieved for doxorubicin (DOX), and the formed GQDs@hMSN(DOX)-PEG NPs showed the feasibility of tumor-oriented drug delivery. The extended retention time in tumor and good drug loading efficacy confirmed that GQDs@hMSN-PEG could serve as one promising candidate for combinational cancer treatment where photodynamic therapy and chemotherapy modules can be integrated into one system.

Due to excellent optical properties, CdTe quantum dots (QDs) exhibit great potential in cancer imaging. However, CdTe QDs can be quickly cleared out before reaching the desired location because of their ultra-small size. The structure and optical properties of CdTe QDs are also easily affected by the surrounding solution, which leads to their compromised applications in vivo. Here, CdTe QDs were incorporated into hollow mesoporous silica nanoparticles (hMSN) to form CdTe@hMSN nano-platforms. The as-synthesized system maintained the excellent emission properties of CdTe QDs; meanwhile, relatively high drug loading efficiency was also observed for doxorubicin (DOX). With the target for vascular endothelial growth factor (VEGF), the formed CdTe@hMSN(DOX)–VEGF Abs showed feasibility of tumor-oriented drug delivery and CdTe@hMSN conjugate accumulation. The high accumulation and enhanced targeted drug delivery of CdTe@hMSN conjugates in tumor nodules confirmed that CdTe@hMSN conjugates can serve as promising candidates for cancer detection and treatment.

CdTe quantum dots (QDs) are considered a potential toxic substance because they contain metal ions. However, most toxicology data are derived from

During the development, dosage optimization and safety evaluation of a drug, rapid and precise monitoring of administered drug and/or its metabolites in biological samples including blood, plasma, serum, tissues and saliva are vital. As drug biotransformation produces more hydrophilic metabolites for the enhancement of drug elimination, which is often a challenge for traditional reversed-phase liquid chromatography (RPLC) separation. Because hydrophilic interaction liquid chromatography (HILIC) is capable of retaining polar compounds and readily compatible with mass spectrometry (MS), HILIC has been used as a complementary separation technique to RPLC for analysis of polar metabolites, especially polar drugs and their metabolites. This review covers core aspects of HILIC-MS/MS method and overall profile of its application in analysis of drug and/or its metabolites. The emphasis of this paper has been placed on the applications of HILIC-MS/MS method in quantitative bioanalysis of drugs alone or along with their metabolites in drug metabolism studies in recent years. As a fundamental and critical step of bioanalytical method, conventional sample preparation techniques of biological matrices for the HILIC-MS/MS analysis of drugs and/or their metabolites are also briefly featured.

A pH-sensitive and double functional nanoprobe was designed and synthesized in a water-soluble system using thioglycolic acid (TGA) and mercapto-acetohydrazide (TGH) as the stabilizers. TGA is biocompatible because the carboxyl group is easily linked to biological macromolecules. At the same time, the hydrazide on TGH reacts with the aldehyde on poly(ethylene glycol) (PEG) and forms a hydrazone bond. The hydrazone bond ruptured at specific pH values and exhibited pH-stimuli-responsive characteristics. As an optical imaging probe, the PEG-TGA/TGH-capped CdTe quantum dots (QDs) had high quality, with a fluorescence efficiency of 25-30%, and remained stable for at least five months. This pH-responsive factor can be used for the effective release of CdTe QDs under the acidic interstitial extracellular environment of tumor cells. This allows the prepared pH-stimuli-responsive nanoprobes to show fluorescence signals for use in cancer cell imaging.

A simple and sensitive liquid chromatography method with diode array detector was established for simultaneous determination of 11 components (geniposidic acid, chlorogenic acid, caffeic acid, geniposide, luteoloside, isochlorogenic acid C, baicalin, luteolin, wogonoside, baicalein and wogonin) in various commercial Yinzhihuang preparations and their herbs by optimizing the extraction, separation and analytical conditions. Eleven components were identified on the basis of their retention times and mass spectra. Chromatographic separation was performed on a C18 analytical column with a gradient elution of acetonitrile and 0.1% formic acid water solution at a flow rate of 1.0 mL/min. The linearity, precision and accuracy of the data obtained were acceptable. The method was used to analyze four Yinzhihuang preparations (powder, capsule, oral liquid and injection) and related herbs (Radix Scutellariae, Flos Lonicerae, Herba Artemisiae Scopariae and Fructus gardeniae). Results suggested that the optimized method could be considered as a good approach to control the quality of Yinzhihuang preparations and their herbs.

A novel method combining electrophoretically mediated microanalysis methodology and partial filling technique was developed and validated for kinetic study of α-chymotrypsin with N-benzoyl-l-tyrosine ethyl ester (l-BTEE) as substrate. The in-line enzymatic reaction was performed in 20 mmol L−1 Tris with 5 mmol L−1 calcium chloride (pH 7.8), while 20 mmol L−1 Tris (pH 7.8) was used as a background electrolyte. A plug–plug injection sequence of incubation buffer, enzyme, substrate, and incubation buffer was applied due to the lower electrophoretic mobility of α-chymotrypsin than that of l-BTEE. The reaction was initiated by the application of 15 kV for 0.2 min. The voltage was turned off to increase the product amount (zero-potential amplification) and turned on again at a constant voltage of 18 kV to separate all the components. Incubation and subsequent analyte separation were carried out in a 37/30 cm (50 μm i.d.) fused-silica capillary at 25 °C. In the developed in-capillary α-chymotrypsin assay, the Michaelis–Menten constant (K m) and an inhibition and activation study were performed. The kinetic parameters are in accordance with that determined by a spectrophotometric method.

Bio oil aqueous two phase systems were formed with ethanol and the salts of (NH4)2SO4, K2HPO4 and NaH2PO4 in bio oil on the ratio of 10:5:10(by mass). After phase separation, both the upper and the lower layers were analyzed by gas column/mass spectrometry (GC/MS). As a result, both K2HPO4/ethanol and NaH2PO4/ethanol system can enrich phenols and levoglucosan in the upperand lower layers,respectly, while NaH2PO4/ethanol system seldom changes the components of bio oil; the (NH4)2SO4/ethanol system is quit different with the other two and we have detected some components with nitrogen. Hence, NaH2PO4/ethanol is an advantage aqueous two phase system for bio oil treatment.

This paper was aimed to study the aqueous two phase extraction (ATPE) on water soluble bio oil(SBO), in which ethanol, K2HPO4, NaH2PO4and (NH4)2SO4were selected to form the water soluble bio oil(SBO) aqueous two phase system (ATPS). After phase separation, the extraction rates and the volume ratios of the upper to lower layer of the ATPSs were investigeted. Both the upper and lower layers of these SBO ATPSs were analyzed by elemental analyzer and Fourier transformation infrared spectrometer (FTIR). The different extraction rates indicates the influnces of different salt during the phase saperation, of which NaH2PO4has less effect to SBO than the other two; K2HPO4may neutralize some organic acid; the lowest extraction rate of ethanol/(NH4)2SO4system indicates the effects of (NH4)2SO4to SBO. Too much ethanol will fech in more water, hence the optimizational ratio of the SBO ATPS should be SBO:salt:ethanol=10:10:5. In element analysis, the diclining of oxygen in all the upper layers and the increasing of nitrogion in both layers of (NH4)2SO4system indicates the abbility of the less oxygen components concentration of the ATPS and the reaction between (NH4)2SO4and SBO. According to FTIR test, the lack of absorption at 1515cm-1of all the lower layers indicates the completely transforming of phenols into the upper layers. Because of the high extraction rate and less influence to SBO, ethanol/NaH2PO4system may be the most suitable ATPS for SBO extraction.