TPGS2k-PLGA composite nanoparticles by depleting lipid rafts in colon cancer cells for overcoming drug resistance.

Recently, studies showed that the drug-resistant cell membranes have formed high-density lipid rafts regions; traditional targeted drug delivery systems can hardly break through the hard shell and deliver drugs to drug-resistant cells. Here, α-tocopherol polyethylene glycol 2000 succinate (TPGS2k) was successfully synthesized and used to modify poly (lactic-glycolic acid) nanoparticles co-loaded with doxorubicin (DOX) and simvastatin (SV) (SV/DOX@TPGS2k-PLGA NPs). The purpose of this study is to explore the synergistic effect between SV consuming cholesterol in lipid rafts and directly down-regulating P-gp expression on the intracellular drugs retention. The research highlights these nanoparticles interrupted lipid rafts (cholesterol-rich domains, where P-gp is often located), which inhibited drug efflux by down-regulating P-gp, promoted the mitochondria apoptosis and made SW620/AD300 cells (DOX-resistant colon cancer cell line) re-sensitized to DOX. Therefore, the carrier can become a promising SV-based nano-delivery system with depleting cholesterol in lipid rafts to reverse drug resistance.

Two-Way Cruise Nanosatellite Promotes Metastasis Inhibition by Immunochemotherapy.

Currently, immunochemotherapy based on tumor-associated macrophages (TAMs) is mainly used for elimination of M2 macrophages. However, these methods cannot make full use of the positive immune-modulatory effects of macrophages. This study explores a two-way cruise strategy for combining immunotherapy based on TAM phenotype reversal with classical chemotherapy, the nanosatellites (DOX@HFn-PGZL@Res) are proposed to accurately deliver the chemotherapeutic agents and immune activators to their respective target cells. When the delivery system is recruited to tumor microenvironment, the nanosatellites are separated into DOX@HFn and Res@GZL nanoparticles, which can enter cancer cells and M2-TAMs, respectively. The data show that DOX@HFn-PGZL@Res successfully re-educate M2 to M1 macrophages, resulting in an activated immune response and inhibition of tumor invasion and metastasis. In general, this work describes a two-way homing nanoplatform for the integration of immunotherapy and chemotherapy, which provides a new idea for the "attack-defense" integrated treatment of tumor.

Chitosan-coated liposome with lysozyme-responsive properties for on-demand release of levofloxacin.

As an anti-infection antibiotic delivery route, a drug-controlled release system based on a specific condition stimulus response can enhance drug stability and bioavailability, reduce antibiotic resistance, achieve on-demand release and improve targeting and utilization efficiency. In this study, chitosan-coated liposomes containing levofloxacin (Lef@Lip@CS) were prepared with lysozyme in body fluids serving as an intelligent "switch" to enable accurate delivery of antibiotics through the catalytic degradation ability of chitosan. Good liposome encapsulation efficacy (64.89 ± 1.86 %) and loading capacity (5.28 ± 0.18 %) were achieved. The controlled-release behavior and morphological characterization before and after enzymatic hydrolysis confirmed that the levofloxacin release rate depended on the lysozyme concentration and the degrees of deacetylation of chitosan. In vitro bacteriostatic experiments showed significant differences in the effects of Lef@Lip@CS before and after enzyme addition, with 6-h inhibition rate of 72.46 % and 100 %, and biofilm removal rates of 51 % and 71 %, respectively. These findings show that chitosan-coated liposomes are a feasible drug delivery system responsive to lysozyme stimulation.

Oxygen-functionalized Fe3O4@o-polypyrrole acting as high-efficiency oxidase mimics and their application in glutathione colorimetric sensing.

The enzyme-like properties of nanozymes may be considerably affected by the structure and surface groups, which thus need to be optimized. Here, through a simple NaOH chemical corrosion method, the chemical structure similar to N-Methylpyrrolidone (NMP), which possessed intrinsic oxidase-like activity, was introduced into polypyrrole (PPy), and then this nanomaterial became oxygen-functionalized PPy (o-PPy) with excellent oxidase-like activity from PPy without this property. Furthermore, after compounding magnetic Fe3O4, the obtained nanocomposites Fe3O4@o-PPy nanoparticles (Fe3O4@o-PPy NPs) showed superiorities in separation during synthesis and real-time control of enzyme catalysis. Studies have found that the enzymatic activity of Fe3O4@o-PPy NPs depended on the amount of functionalized oxygen and the conjugation extent of o-PPy. Fe3O4@o-PPy NPs had efficient oxidase-like activity under a wide range of pH and temperature. Based on the oxidase-like activity of Fe3O4@o-PPy NPs, a colorimetric sensor for glutathione (GSH), which presented rich color changes and satisfactory colorimetric resolution by adding the amaranth, was realized. We believe that the functional modification and structural regulation of PPy can not only realize its wider application but also promote the discovery of novel and efficient nanozymes.

Electrochemical Biosensor Based on HRP/Ti3C2/Nafion Film for Determination of Hydrogen Peroxide in Serum Samples of Patients with Acute Myocardial Infarction.

Hydrogen peroxide (H2O2) has been reported to mediate a variety of physiological and pathological processes in living systems. In this work, a biosensor for determination of H2O2 was prepared by using an HRP/Ti3C2/Nafion film-modified glassy carbon electrode (GCE). Ti3C2 nanosheets with remarkable conductivity and high specific surface area were chosen as carriers for HRP. Moreover, this biosensor modified with HRP has a specific catalytic effect on H2O2. The difference in peak current could reflect the quantitative change of H2O2. The linear range of the biosensor is 5-8000 µM, and the detection limit is 1 µM (S/N = 3). This biosensor was used to detect H2O2 in clinical serum samples of normal controls and patients with acute myocardial infarction (AMI) before and after percutaneous coronary intervention (PCI). The results showed that the difference between normal controls and patients is significant (P < 0.05), as well as the difference for patients before and after PCI (P < 0.01), but no significant difference existed between postoperative patients and normal controls. This biosensor has the advantages of simple preparation, high sensitivity, and quick detection, showing potential application in clinical diagnosis.

Magnetic sensing film based on Fe3O4@Au-GSH molecularly imprinted polymers for the electrochemical detection of estradiol.

A novel magnetic molecularly imprinted sensing film (MMISF) was fabricated for the determination of estradiol (E2) based on magnetic glassy carbon electrode (MGCE) and magnetic molecularly imprinted polymers (MMIPs). The MMIPs were synthesized by in situ polymerization of glutathione (GSH)-functionalized gold (Au)-coated Fe3O4 (Fe3O4@Au-GSH) nanocomposites and aniline. The MMISF was constructed with MMIPs via a kind of "soft modification" where MMIPs were assembled and immobilized on the surface of MGCE or removed from it by freely installing a magnet into MGCE or not. The E2-MMIPs were obtained by MMIPs recognizing E2 from sample, and the electrochemical detection was carried out after forming the "soft modification" sensing film by putting MGCE into the E2-MMIPs suspension liquid. Afterwards, the "soft modification" MMISF was peeled off from the electrode by removing the magnet from MGCE. The interface of the electrode could be quickly refreshed through simple treatment for the next detection. The structures and morphologies of Fe3O4@Au-GSH, MMIPs and MMISF were investigated by Fourier transform infrared spectrometer, ultraviolet and visible spectrophotometer, scanning electron microscope and atomic force microscope. In addition, the MMISF was successfully used for detecting E2 in milk powder with good sensitivity, selectivity, reproducibility and efficiency. The linear range of the MMISF for E2 was 0.025-10.0µmolL(-1) with the limit of detection of 2.76nmolL(-1) (S/N= 3).

Fe3O4@rGO doped molecularly imprinted polymer membrane based on magnetic field directed self-assembly for the determination of amaranth.

Based on magnetic field directed self-assembly (MDSA) of Fe3O4@rGO composites, a novel magnetic molecularly imprinted electrochemical sensor (MIES) was fabricated and developed for the determination of the azo dye amaranth. Fe3O4@rGO composites were obtained by a one-step approach involving the initial intercalating of iron ions between the graphene oxide layers via the electrostatic interaction, followed by the reduction with hydrazine hydrate to deposit Fe3O4 nanoparticles onto the reduced oxide graphene nanosheets. In molecular imprinting, the complex including the function monomer of aniline, the template of amaranth and Fe3O4@rGO was pre-assembled through π-π stacking and hydrogen bonding interactions, and then was self-assembled on the surface of magnetic glassy carbon electrode (MGCE) with the help of magnetic field induction before electropolymerization. The structures and morphologies of Fe3O4@rGO and the doped molecularly imprinted polymers (MIPs) were investigated by Fourier transform infrared spectrometer (FT-IR), Raman spectra and scanning electron microscope (SEM). Besides, the characterization by differential pulse voltammetry (DPV) showed that Fe3O4@rGO composites promoted the electrical conductivity of the imprinted sensors when doped into the MIPs. The adsorption isotherms and adsorption kinetics were employed to evaluate the performances of MIES. The detection of amaranth was achieved via the redox probe K3[Fe(CN)6] by blocking the imprinted cavities, which avoided the interferences of oxidation products and analogs of amaranth. Furthermore, the prepared MIES exhibited good sensitivity, selectivity, reproducibility and efficiency for detecting amaranth in fruit drinks. The average recoveries were 93.15-100.81% with the RSD <3.0%.