Enhanced Efficacy against Drug-Resistant Tumors Enabled by Redox-Responsive Mesoporous-Silica-Nanoparticle-Supported Lipid Bilayers as Targeted Delivery Vehicles.

Multidrug resistance (MDR) is frequently induced after long-term exposure to reduce the therapeutic effect of chemotherapeutic drugs, which is always associated with the overexpression of efflux proteins, such as P-glycoprotein (P-gp). Nano-delivery technology can be used as an efficient strategy to overcome tumor MDR. In this study, mesoporous silica nanoparticles (MSNs) were synthesized and linked with a disulfide bond and then coated with lipid bilayers. The functionalized shell/core delivery systems (HT-LMSNs-SS@DOX) were developed by loading drugs inside the pores of MSNs and conjugating with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and hyaluronic acid (HA) on the outer lipid surface. HT-LMSNs-SS and other carriers were characterized and assessed in terms of various characteristics. HT-LMSNs-SS@DOX exhibited a dual pH/reduction responsive drug release. The results also showed that modified LMSNs had good dispersity, biocompatibility, and drug-loading capacity. In vitro experiment results demonstrated that HT-LMSNs-SS were internalized by cells and mainly by clathrin-mediated endocytosis, with higher uptake efficiency than other carriers. Furthermore, HT-LMSNs-SS@DOX could effectively inhibit the expression of P-gp, increase the apoptosis ratios of MCF-7/ADR cells, and arrest cell cycle at the G0/G1 phase, with enhanced ability to induce excessive reactive oxygen species (ROS) production in cells. In tumor-bearing model mice, HT-LMSNs-SS@DOX similarly exhibited the highest inhibition activity against tumor growth, with good biosafety, among all of the treatment groups. Therefore, the nano-delivery systems developed herein achieve enhanced efficacy towards resistant tumors through targeted delivery and redox-responsive drug release, with broad application prospects.

Bionic Scarfskin-Inspired Hierarchy Configuration toward Tunable Microwave-Absorbing Performance.

Maintaining the dynamical microwave synchronization between a target and its background is the key to electromagnetical invisibility in real environment. Herein, we introduce an archetypical paradigm for ultraelastic films of graphene-functionalized ionic gel with tunable microwave-absorbing behaviors. Inspired by the local structural changes during the wing-spreading process of vespertilionids, the experimental and finite element simulations have revealed that proper shape changing of 3D wrinkled structure containing ridge walls with moderate impedance is the effective way to minimize reflected wave and promote energy attenuation. An optimal RL value of -43.6 dB and valid regulatory amplitude of 41.5 dB, covering a microwave-absorbing to shielding state, could be reached with only 0.2% weight fraction of the active ingredient RGO filler. The significant regulatory performance is attributed to the competitive effect between intrinsic dielectric attenuation of silicon nitride modified reduced graphene oxide (RGO-SiN), multiscattering of a 3D wrinkled structure, and evolution of the oriented RGO-SiN.

Photoelectric response properties under UV/red light irradiation of ZnO nanorod arrays coated with vertically aligned MoS2 nanosheets.

MoS2 with layered structure and distinct physical properties has attracted attention for electronic or optoelectronic devices. The photoelectric response properties of MoS2/ZnO heterojunctions based devices fabricated by spin-coating MoS2 nanosheets solutions on ZnO nanorod arrays (NRs) were investigated. The results revealed that MoS2 nanosheets were vertically aligned on the surface of ZnO NRs and the devices exhibit good photoresponse stability and reproducibility under UV and red light illuminations. The vertically aligned MoS2 nanosheets facilitate the fast photogenerated carrier separation and transport. The devices with few-layered MoS2 nanosheets show a high responsivity and detectivity under UV and red light illuminations, which can be attributed to small contact resistance between MoS2 nanosheets and ZnO NRs. These results provide important insights in the facile fabrication strategy and understanding electronic and optoelectronic devices based on the heterostructures with vertically aligned MoS2.

Study of ibuprofen glucopyranoside derivative synthesis by Candida antarctica lipase in organic solvent.

The direct esterification of ibuprofen and methyl alpha-D-glucopyranoside in organic solvent by Novozym 435 was investigated in terms of the main variables controlling the process, including initial water activity (a(w), 0.05-0.75), incubation time, (0-168 h) and substrate concentration. The results showed that the lower initial aw values resulted in higher enzymatic activity and bioconversion yield. The most appropriate initial aw and incubation time were 0.06 and 144 h, respectively. The results also showed that the optimal ratio of ibuprofen to methyl alpha-D-glucopyranoside was 2.0. By optimizing these parameters, the yield increased about 50%. In addition, the product was confirmed to be methyl 6-O-(2'-(4'-isobutylphenyl) propionyl) D-alpha-glucopyranoside.

Pharmacological activity and hydrolysis behavior of novel ibuprofen glucopyranoside conjugates.

Novel ester prodrugs (II, III and IV) of ibuprofen (I) were synthesized using alpha-methyl, ethyl and propyl glucopyranoside as promoieties and tested for their anti-inflammatory, analgesic and ulcerogenic activities. Study of their chemical hydrolysis in aqueous buffer (pH 3.0-10.0) showed that these compounds acted as true prodrugs of ibuprofen, giving the ibuprofen and alkyl glucopyranoside. Additionally, all the derivatives studied did cleave rapidly inside the biological system and on oral administration did elicit a pharmacological profile quite similar to that of ibuprofen, but, unlike this drug, they displayed reduced gastric ulceration. In conclusion, these alkyl glucopyranoside esters have promising properties as prodrugs for oral delivery of ibuprofen.

Immobilization of permeabilized whole cell penicillin G acylase from Alcaligenes faecalis using pore matrix crosslinked with glutaraldehyde.

The activity of penicillin G acylase from Alcaligenes faecalis increased 7.5-fold when cells were permeabilized with 0.3% (w/v) CTAB. The treated cells were entrapped by polyvinyl alcohol crosslinked with boric acid, and crosslinked with 2% (v/v) glutaraldehyde to increase the stability. The conversion yield of penicillin G to 6-aminopenicillanic acid was 75% by immobilized system in batch reaction. No activity was lost after 15 cycles and about 65% enzyme activity was retained at the end of the 31th cycle.