Brain gliomas: Diagnostic and therapeutic issues and the prospects of drug-targeted Nano-delivery technology.

Glioma is the most common intracranial malignant tumor, with severe difficulty in treatment and a low patient survival rate. Due to the heterogeneity and invasiveness of tumors, lack of personalized clinical treatment design, and physiological barriers, it is often difficult to accurately distinguish gliomas, which dramatically affects the subsequent diagnosis, imaging treatment, and prognosis. Fortunately, nano-delivery systems have demonstrated unprecedented capabilities in diagnosing and treating gliomas in recent years. They have been modified and surface modified to efficiently traverse BBB/BBTB, target lesion sites, and intelligently release therapeutic or contrast agents, thereby achieving precise imaging and treatment. In this review, we focus on nano-delivery systems. Firstly, we provide an overview of the standard and emerging diagnostic and treatment technologies for glioma in clinical practice. After induction and analysis, we focus on summarizing the delivery methods of drug delivery systems, the design of nanoparticles, and their new advances in glioma imaging and treatment in recent years. Finally, we discussed the prospects and potential challenges of drug-delivery systems in diagnosing and treating glioma.

The innovative design of a delivery and real-time tracer system for anti-encephalitis drugs that can penetrate the blood-brain barrier.

As a "wall" between blood flow and brain cells, the blood-brain barrier (BBB) makes it really difficult for drugs to cross this barrier and work. This is particularly the case for pharmaceuticals of acute encephalitis therapies, largely excluded from the brain following systemic administration. Herein we report an advanced drug delivery system that can cross the BBB and target acute inflammation based on the controlled release of macrophage-camouflaged glow nanoparticles via a Trojan horse strategy. Benefiting from afterglow imaging that eliminates background interference and RAW 264.7 cells (RAW) with special immune homing and long-term tracking capabilities, polydopamine (PDA)-modified afterglow nanoparticles (ANPs) as near-infrared photo-responsive drug carriers in a controlled delivery system camouflaged by macrophages can penetrate the BBB by crossing the intercellular space and trigger the anti-inflammatory drug by photothermal conversion in the brain parenchyma dexamethasone (Dex) release, exhibiting good acute inflammation recognition and healing ability. APD@RAW was monitored to cross the BBB and image deep brain inflamed areas in a model of acute brain inflammation. Meanwhile, the delivered Dex mitigated the brain damage caused by inflammatory cytokines secretion (IL-6, TNF-α, and IL-1ß). Overall, this drug delivery system holds excellent potential for BBB penetrating and acute encephalitis therapies.

Chemically defined stem cell microniche engineering by microfluidics compatible with iPSCs' growth in 3D culture.

The development of induced pluripotent stem cell (iPSCs) has opened unprecedented opportunities for biomedical applications, but poorly defined animal-derived matrices yield cells with limited therapeutic value. Considerable challenges remain in improving cell-culturing approaches to create the conditions for iPSCs' reliable expansion. Herein we report the development of a chemically defined, artificial three-dimensional (3D) microniche for iPSCs' growth and reliable expansion, constructed with degradable polyethyleneglycol-co-polycaprolactone and RGDfk-functionalized dendritic polyglycerol precursors according to bioorthogonal strain-promoted azide-alkyne cycloaddition by droplet-based microfluidics. This compatible microniche can allow for the robust production of iPSCs that maintain high pluripotency expression and excellent viability without pathogen or immunogen transfer risks. This microniche technology shows great promise in enabling iPSCs to achieve their full therapeutic potential.

Matrix Stiffness Regulates Chemosensitivity, Stemness Characteristics, and Autophagy in Breast Cancer Cells.

The biomechanical environment of natural or synthetic extracellular matrices (ECMs) is identified to play a considerable role in embryonic development in stem cell fate and also in cancer development and fibrotic diseases. However, rare evidence shows the impact of biomechanical signals such as ECM stiffness on cancer cell stemness and autophagy, which makes huge contributions to cancer and many developmental and physiological processes. Furthermore, the influence and mechanism of ECM stiffness on autophagy in cancer cells remains unclear. Herein, we employed fibronectin-coated polyacrylamide hydrogels as the substrates for culturing breast cancer cells. We found that a soft environment was beneficial for the maintenance of cancer stem cell (CSC) population in breast cancer cells, which likely led to aggravated chemoresistance. Conversely, nutritional deprivation-induced autophagy was elevated along with increasing matrix stiffness. In addition, we found that though the central regulator of mechanotransduction, the yes-associated protein, YAP, was beneficial for autophagy activation, unexpectedly, it was not the main cause of rigid substrate promoting autophagy. In contrast, the YAP was crucial for a compliant environment for maintaining breast cancer stem cells and promoting chemotherapeutic resistance. We also found that the Rho-ROCK-ERK signal pathway and actin cytoskeleton were essential for the regulation of autophagy by matrix stiffness. Taken together, our study showed the important influence of ECM stiffness on stemness and autophagy in breast cancer cells and revealed the possible signal pathway involved in the mechanotransduction in autophagy activation, which provides significant implications for the study of cancer progression and design of hydrogels for tissue engineering in clinical therapy.

Detection of DNA utilizing a fluorescent reversible change of a biosensor based on the electron transfer from quantum dots to polymyxin B sulfate.

A fluorescent "turn off-on" pattern for the detection of herring sperm DNA (hsDNA) had been designed through utilizing the interaction between polymyxin B sulfate (PMBS) and hsDNA as an inherent performance and the fluorescent transformation of glutathione (GSH)-capped CdTe quantum dots (QDs) as an external manifestation. Due to the occurrence of the photoinduced electron transfer from the QDs to PMBS, the fluorescence of GSH-capped CdTe QDs could be effectively quenched by PMBS, causing the system into "off" state. With the addition of hsDNA, the quenched fluorescence of GSH-capped CdTe QDs could be restored for the reason that PMBS embedded into hsDNA double helix structure to form new complex and peeled off from the surface of GSH-capped CdTe QDs, leading the system into "on" condition. Corresponding experimental results illustrated that the relative recovered fluorescence intensity of GSH-capped CdTe QDs-PMBS system was near proportional to the concentration of hsDNA within the range of 0.059-15.0 µg mL(-1). This proposed method demonstrated a good linear correlation coefficient of 0.9937 and a detection limit (3 σ/K) of 0.018 µg mL(-1) for hsDNA. This dual-directional fluorescent biosensor overcame the selectivity problem commonly existed in the traditional mono-directional fluorescence detection mode and owned perfect analysis applications in biochemical DNA monitoring.

Highly sensitive fluorescence biosensors for sparfloxacin detection at nanogram level based on electron transfer mechanism of cadmium telluride quantum dots.

A sensitive fluorescence biosensor for determining sparfloxacin (SPF) based on the electron transfer mechanism and the fluorescence quenching effect of SPF to cadmium telluride quantum dots (CdTe QDs) was developed. The mechanism of the interaction between SPF and CdTe QDs was investigated by UV/Vis absorption and fluorescence spectroscopy. The biosensor could be used for the determination of SPF with a high sensitivity. Under optimum conditions, the linear range was from 0.28 to 40 µg SPF ml(-1) with a correlation coefficient of 0.9983, and the detection limit (3δ/k) was 83.7 ng SPF ml(-1). Furthermore, this method has been applied to the determination of SPF in the synthetic environmental water samples and the spiked human serum samples with good results.

Fluorescent reversible regulation based on the interactions of topotecan hydrochloride, neutral red and quantum dots.

The interactions of topotecan hydrochloride (THC), neutral red (NR) and thioglycolic acid (TGA) capped CdTe/CdS quantum dots (QDs) built a solid base for the controlling of the fluorescent reversible regulation of the system. This study was developed by means of ultraviolet-visible (UV-vis) absorption, fluorescence (FL), resonance Rayleigh scattering (RRS) spectroscopy and transmission electron microscopy (TEM). Corresponding experimental results revealed that the fluorescence of TGA-CdTe/CdS QDs could be effectively quenched by NR, while the RRS of the QDs enhanced gradually with the each increment of NR concentration. After the addition of THC, the strong covalent conjugation between NR and THC which was in carboxylate state enabled NR to be dissociated from the surface of TGA-CdTe/CdS QDs to form more stable complex with THC, thereby enhancing the fluorescence of the TGA-CdTe/CdS QDs-NR system. What is more, through analyzing the optical properties and experimental data of the reaction between TGA-CdTe/CdS QDs and NR, the possible reaction mechanism of the whole system was discussed. This combination of multiple spectroscopic techniques could contribute to the investigation for the fluorescent reversible regulation of QDs and a method could also be established to research the interactions between camptothecin drugs and dyes.