Aminoglucose-functionalized, redox-responsive polymer nanomicelles for overcoming chemoresistance in lung cancer cells.

BACKGROUND: Chemotherapeutic drugs used for cancer therapy frequently encounter multiple-drug resistance (MDR). Nanoscale carriers that can target tumors to accumulate and release drugs intracellularly have the greatest potential for overcoming MDR. Glucose transporter-1 (GLUT-1) and glutathione (GSH) overexpression in cancer cells was exploited to assemble aminoglucose (AG)-conjugated, redox-responsive nanomicelles from a single disulfide bond-bridged block polymer of polyethylene glycol and polylactic acid (AG-PEG-SS-PLA). However, whether this dual functional vector can overcome MDR in lung cancer is unknown. RESULTS: In this experiment, AG-PEG-SS-PLA was synthetized successfully, and paclitaxel (PTX)-loaded AG-PEG-SS-PLA (AG-PEG-SS-PLA/PTX) nanomicelles exhibited excellent physical properties. These nanomicelles show enhanced tumor targeting as well as drug accumulation and retention in MDR cancer cells. Caveolin-dependent endocytosis is mainly responsible for nanomicelle internalization. After internalization, the disulfide bond of AG-PEG-SS-PLA is cleaved in the presence of high intracellular glutathione levels, causing the hydrophobic core to become a polar aqueous solution, which subsequently results in nanomicelle disassembly and the rapid release of encapsulated PTX. Reduced drug resistance was observed in cancer cells in vitro. The caspase-9 and caspase-3 cascade was activated by the AG-PEG-SS-PLA/PTX nanomicelles through upregulation of the pro-apoptotic proteins Bax and Bid and suppression of the anti-apoptotic protein Bcl-2, thereby increasing apoptosis. Furthermore, significantly enhanced tumor growth inhibition was observed in nude mice bearing A549/ADR xenograft tumors after the administration of AG-PEG-SS-PLA/PTX nanomicelles via tail injection. CONCLUSIONS: These promising results indicate that AG-PEG-SS-PLA/PTX nanomicelles could provide the foundation for a paradigm shift in MDR cancer therapy.

The characterization and analysis of the compound hemostatic cotton based on Ca2+/poly (vinyl alcohol)/soluble starch-fish skin collagen.

Accidental bleeding is an unavoidable problem in daily life. To avoid the risk of excessive blood loss, it is urgent to design a functional material that can quickly stop bleeding. In this study, an efficient wound dressing for hemostasis was investigated. Based on the characteristics that Ca2+ and fish skin collagen (FSC) could activate the coagulation mechanism, hemostatic cotton was prepared by solvent replacement method using CaCl2, FSC, soluble starch (SS), and polyvinyl alcohol (PVA) as raw materials. The cytotoxicity test showed the Ca2+PVA/FSC-SS hemostatic cottons had good biocompatibility. The activated partial thromboplastin time (APTT) of Ca2+PVA/FSC-SS(4) was 35.34 s, which was 22.07 s faster than that of PVA/FSC-SS, indicating Ca2+PVA/FSC-SS mediated the endogenous coagulation system. In vitro coagulation test, Ca2+PVA/FSC-SS(4) could stop bleeding rapidly within 39.60 ± 5.16 s, and the ability of wound healing was higher than commercial product (Celox). This study developed a rapid procoagulant and hemostatic material, which had a promising application in a variety of environments.

Liquefied Polysaccharides-Based Polymer with Tunable Condensed State Structure for Antimicrobial Shield by Multiple Processing Methods.

The phase behavior of biomolecules containing persistent molecular entities is generally limited due to their characteristic size that exceeds the intermolecular force field. Consequently, favorable properties normally associated with the liquid phase of a substance, such as fluidity or processability, are not relevant for the processing of biomolecules, thus hindering the optimal processing of biomolecules. The implied problem that arises is how to convert folded biomolecules to display a richer phase behavior. To alleviate this dilemma, a generic approach to liquefied polysaccharides-based polymers is proposed, resulting in a polysaccharide fluid with a tunable condensed state structure (solid-gel-liquid). Polysaccharide biobased fluids materials transcend the limits of the physical state of the biobased material itself and can even create completely new properties (different processing methods as well as functions) in a variety of polymeric structures. Considering the solvent incompatible high and low-temperature applications, this method will have a great influence on the design of nanostructures of biomolecular derivatives and is expected to transform biomass materials such as polysaccharide biopolymers from traditional use to resource use, ultimately leading to the efficient use of biomass materials and their sustainability.

Flow-induced translocation of polymers through a fluidic channel: a dissipative particle dynamics simulation study.

The dynamics of flow-induced translocation of polymers through a fluidic channel has been studied by dissipative particle dynamics (DPD) approach. Unlike implicit solvent models, the many-body energetic and hydrodynamic interactions are preserved naturally by incorporating explicit solvent particles in this approach. The no-slip wall boundary and the adaptive boundary conditions have been implemented in the modified DPD approach to model the hydrodynamic flow within a specific wall structure of fluidic channel and control the particles' density fluctuations. The results show that the average translocation time versus polymer chain length satisfies a power-law scaling of τ ∼N(1.152). The conformational changes and translocation dynamics of polymers through the fluidic channel have also been investigated in our simulations, and two different translocation processes, i.e., the single-file and double-folded translocation events, have been observed in detail. These findings may be helpful in understanding the conformational and dynamic behaviors of such polymer and/or DNA molecules during the translocation processes.

Liquefaction of starch using solid-acid catalysts derived from spent coffee for the production of plasticized poly (vinyl alcohol) films.

This paper reports a strategy for preparing polyether polyols from corn starch, with (i) a mixture of polyethylene glycol 400 and glycerin (7:3, w/w) as the liquefying solvent and (ii) a spent-coffee-derived solid-acid catalyst (SC-SAC) (1:10, w/w, SC-SAC/starch) at 433 K for 1.5 h, under which conditions the liquefaction yield exceeded 99 %. The SC-SAC was prepared via hydrothermal carbonization at 453 K for 12 h, followed by sulfonation with H2SO4 at 343 K for 10 h. The liquefied starch product (SLP) was then used to plasticize poly(vinyl alcohol) (PVA) films with various mixing ratios. The optimal 0.4 SLP/PVA blend film exhibited good mechanical properties (tensile strength 38.07 MPa, elongation at break 1199 %), good transparency, and excellent flexibility. The results highlight the possibility of using SLP/PVA films in the development of degradable packaging materials.

Field-Free Isolation of Exosomes from Extracellular Vesicles by Microfluidic Viscoelastic Flows.

Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30-200 nm) poses serious challenges in their isolation from complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we present a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive in the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The proposed technique may serve as a versatile platform to facilitate exosome analyses in diverse biochemical applications.