Acid-Activated Melittin for Targeted and Safe Antitumor Therapy.

Melittin (MLT), as a natural active biomolecule, can penetrate the tumor cell membrane to play a role in cancer treatment and will attract more attention in future development of antitumor drugs. The main component of natural bee venom MLT was modified by introducing a pH-sensitive amide bond between the 2,3-dimethyl maleimide (DMMA) and the lysine (Lys) of MLT (MLT-DMMA). MLT and its corresponding modified peptide MLT-DMMA were used for antitumor and biocompatibility validation. The biomaterial characteristics were tested by MALDI-TOF MS, 1H NMR, IUPAC and HPLC, cell viability, hemolytic and animal experiment safety evaluation. Compared with the primary melittin, the modified peptide showed decreased surface charge and low cytotoxicity in physiological conditions. Moreover, cell assays confirmed the acid-activated conversion of amide bond resulting in adequate safety during delivery and timely antitumor activity in tumor lesions. Thus, MLT-DMMA provided a feasible platform to improve the targeted and safe antitumor applications.

Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications.

Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed.

Dual tumor-targeted poly(lactic-co-glycolic acid)-polyethylene glycol-folic acid nanoparticles: a novel biodegradable nanocarrier for secure and efficient antitumor drug delivery.

Further specific target-ability development of biodegradable nanocarriers is extremely important to promote their security and efficiency in antitumor drug-delivery applications. In this study, a facilely prepared poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-folic acid (FA) copolymer was able to self-assemble into nanoparticles with favorable hydrodynamic diameters of around 100 nm and negative surface charge in aqueous solution, which was expected to enhance intracellular antitumor drug delivery by advanced dual tumor-target effects, ie, enhanced permeability and retention induced the passive target, and FA mediated the positive target. Fluorescence-activated cell-sorting and confocal laser-scanning microscopy results confirmed that doxorubicin (model drug) loaded into PLGA-PEG-FA nanoparticles was able to be delivered efficiently into tumor cells and accumulated at nuclei. In addition, all hemolysis, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, and zebrafish-development experiments demonstrated that PLGA-PEG-FA nanoparticles were biocompatible and secure for biomedical applications, even at high polymer concentration (0.1 mg/mL), both in vitro and in vivo. Therefore, PLGA-PEG-FA nanoparticles provide a feasible controlled-release platform for secure and efficient antitumor drug delivery.

Effervescent-salt-assisted dispersive micro-solid-phase extraction using mesoporous hybrid materials coupled with ultra-performance liquid chromatography for the determination of trace-level compounds in complicated plant preparations.

A novel effervescent-salt-assisted dispersive micro-solid-phase extraction using mesoporous hybrid materials was developed for the extraction of minute traces of constituents in complicated plant preparations. In this study, a special tablet containing carbon dioxide sources (sodium dihydrogenphosphate and sodium carbonate) and the sorbent (mesoporous hybrid materials) was prepared. The effects of different parameters influencing the extraction efficiency such as the concentration of salts, the type and concentration of mesoporous material, pH of diluent, and desorption solvents were investigated and optimized. Results show that the proposed method using green solvents (water) as extraction solutions required low consumption of sample amount and obtained high enrichment efficiency. Moreover, under optimized conditions, the tested tanshinones exhibited good linearity (r(2) > 0.994) in the concentration range of 0.5 to 80 ng mL(-1). The limits of detection values were lower than 0.0803 pg using UV-visible detection. The developed method was successfully applied for the analysis of trace tanshinones in compound Danshen dripping pill and Danqi tablet samples.

Ionic-liquid-micelle-functionalized mesoporous Fe3O4 microspheres for ultraperformance liquid chromatography determination of anthraquinones in dietary supplements.

A magnetic solid-phase extraction method using ionic liquid (IL)-micelle-functionalized mesoporous Fe3O4 microspheres (MFMs) was proposed for the preconcentration of anthraquinones in dietary supplements. The analytes were then determined by ultraperformance liquid chromatography combined with an ultraviolet detector. The extraction parameters, such as the choice of ILs, the concentrations of ILs and MFMs, the pH of diluent, and the concentration of acetic acid in the eluent, were presented. Under the optimized conditions, the limits of detection and limits of quantitation were 0.4-2.8 ng mL(-1) and 1.4-9.4 ng mL(-1), respectively. The accuracy of the proposed method was investigated by recovery in herb and granules of Radix et Rhizoma Rhei, yielding values between 89.25% and 96.48%. The use of the proposed method in the sample pretreatment of complex dietary supplements is feasible due to the high surface area and excellent adsorption capacity of MFMs after modification with IL.

Highly sensitive analysis of flavonoids by zwitterionic microemulsion electrokinetic chromatography coupled with light-emitting diode-induced fluorescence detection.

A rapid zwitterionic microemulsion electrokinetic chromatography (ZI-MEEKC) approach coupled with light-emitting-diode-induced fluorescence (LED-IF, 480nm) detection was proposed for the analysis of flavonoids. In the optimization process, we systematically investigated the separation conditions, including the surfactants, cosurfactants, pH, buffers and fluorescence parameters. It was found that the baseline separation of the seven flavonoids was obtained in less than 5min with a running buffer consisting of 92.9% (v/v) 5mM sodium borate, 0.6% (w/v) ZI surfactant, 0.5% (w/v) ethyl acetate and 6.0% (w/v) 1-butanol. High sensitivity was obtained by the application of LED-IF detection. The limits of detection for seven flavonoids were in the range of 3.30×10(-8) to 2.15×10(-6)molL(-1) without derivatization. Ultimately, the detection method was successfully applied to the analysis of flavonoids in hawthorn plant and food products with satisfactory results.

Ionic liquid-based one-step micellar extraction of multiclass polar compounds from hawthorn fruits by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

An ionic liquid (IL)-based one-step micellar extraction procedure was developed for the extraction of multiclass polar analytes (protocatechuic acid, chlorogenic acid, epicatechin, hyperoside, isoquercitrin, quercetin) from hawthorn fruits and their determination using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Compared to conventional organic solvent extractions, this newly proposed method was much easier, more sensitive, environmentally friendly, and effective as well. Several important parameters influencing the micellar extraction efficiency are discussed, such as selection of ILs, surfactant concentration, and extraction time. Under the optimal conditions, good linearity was achieved for each analyte with correlation coefficients (r(2)) ranging from 0.9934 to 0.9999, and the recovery values ranged from 89.3 to 106% with relative standard deviations lower than 5.5%. Results suggest that the IL-based one-step micellar extraction could be an alternative and promising means in future food analysis.

Enhanced separation of Compound Xueshuantong capsule using functionalized carbon nanotubes with cationic surfactant solutions in MEEKC.

A novel additive of multi-walled carbon nanotubes (MWNTs) dispersed with cationic surfactants or mixed cationic/anionic surfactants was used for MEEKC separation of eight phenolic compounds, four glycosides, and one phenanthraquinone. In this context, several parameters affecting MEEKC separation were studied, including the dispersion agents of MWNTs, MWNTs content, oil type, SDS concentration, and the type and concentration of cosurfactant. Compared with conventional MEEKC, the addition of all types of MWNTs dispersions using single or mixed cationic surfactant solutions in running buffers was especially useful for improving the separation of solutes tested, as they influenced the partitioning between the oil droplets and aqueous phase due to the exceptional electrical properties and large surface areas of MWNTs. Use of cationic surfactant-coated MWNTs (6.4 µg/mL) as the additive in a microemulsion buffer (0.5% octanol, 2.8% SDS, 5.8% isopropanol, and 5 mM borate buffer) yielded complete resolution of 13 analytes. The proposed method has been successfully applied for the detection and quantification of the studied compounds in a complex matrix sample (Compound Xueshuantong capsule).