The cellular uptake of drug carriers to the cytosol of a specific cell remains challenging, and a non-classical supramolecular strategy is motivated. Here, we select a model host-guest complex in which a diamino-viologen (VG) fluorescent tag was engulfed by cucurbituril (CB8) and covalently linked to alginate polysaccharides (ALG) as the modified drug vehicle. When adsorbed on the ALG surface, the encapsulation of VG was first confirmed utilizing FTIR and NMR spectroscopic methods. Solid optical measurements (DRS, PL, and TRPL) revealed emissive materials at around 650 nm and that CB8 enhanced the rigidity of the modified hydrogel. The molar composition of 2 to 1 for the complexation of VG to CB8 on the alginate surface and the thermal stabilities were also confirmed using TGA and DSC techniques. CB8 induced a dramatic decrease in the average size of the VGALG polysaccharides from 485 to 165 nm and a turnover in their charge from -19.8 to +14.4 mV. Flow cytometry with inhibitors of various endocytosis pathways was employed to track the cellular uptake across different blood cell types: human T-cell leukemia 1301 and peripheral blood mononuclear cells. Noticeably, complexation of VG to CB8 host on top of the sugar platform dramatically enhanced the internalization to 1301 cells (viz. from 1 to 99%) at a concentration of 1.8 mg/mL via caveolae-mediated endocytosis (CvME) because of the size reduction, turnover in the charge from negative to positive, and rigidity induction. These observations reveal a more profound understanding of the macrocyclic effects on drug delivery
Alzheimers disease (AD) is a common neurodegenerative disease. The histopathological changes of AD include amyloid β-protein (Aβ) deposition, tau tangles, neuroinflammation and neurodegeneration. Some of the pathological changes could be shown in vivo by positron emission tomography (PET) and magnetic resonance imaging (MRI) biomarkers which play a key role in diagnosing AD. Fluorodeoxyglucose positron emission tomography (FDG-PET) can reflect and predict dysfunction. Aβ-PET was sensitive for the diagnosis of early AD but cannot distinguish the severity of AD. Tau-PET can compensate for the deficiency of Aβ-PET. Tau tangles were positively correlated with the severity of AD, and also associated with cognitive impairment. Probes targeting neuroinflammation of AD have been developed, but further study is needed to validate its effectiveness. Conventional MRI performs high tissue contrast that can show structural changes and has been routinely applied in clinical practice, such as evaluation of cerebral atrophy. Advanced MRI sequences (such as DTI、ASL、MRS、BOLD and QSM) that can provide additional information beyond structure that includes brain microstructure, blood perfusion, metabolite concentration, brain activity, connections and networks between brain regions, iron deposition, etc. The integrated PET and MR may improve the diagnostic efficiency of AD.
Organoids are three-dimensional cell aggregates with near-physiologic cell behaviors and can undergo long-term expansion in vitro. They are amenable to high-throughput drug screening processes, which renders them a viable preclinical model for drug development. The procedure of organoid-based high-throughput screening has been extensively employed to discover small molecule drugs, encompassing the steps of generating organoids, examining efficient drugs in organoid cultures, and data assessment. Compared to small molecules, peptides are more straightforward to synthesize, can be modified chemically, and demonstrate a high degree of target specificity and low cytotoxicity. Therefore, they have emerged as promising carriers to deliver drugs to disease-associated targets, and could be efficient therapeutic drugs for various diseases. To date, organoids have been used to evaluate the efficacy of certain peptide agents; however, no organoid-based high-throughput screening of peptide drugs has been reported. Given the advantages of peptide drugs, there is an urgent need to establish organoid-based peptide high-throughput screening platforms. In this review, we discuss the typical approach of screening small-molecular drugs with the use of organoid cultures, as well as provide an overview of the studies that have incorporated organoids in peptide research. Drawing on the knowledge gained from small molecular screens, we explore the difficulties and potential avenues for creating new platforms to identify peptide agents using organoid models.
Biosafe wearable healthcare monitor has attracted significant attention owing to their applicability to wearable electronics. However, the narrow sensing range and poor response limit the application of flexible devices for comprehensive monitoring of human health-related physiological signals (i.e. pulse diagnosis). Critical challenges remain in the development of biocompatible materials and the design of flexible bio-integrated platforms for these purposes, targeting performance approaching those of conventional wafer-based technologies and long-term operational stability. In this context, this work presents a robust and flexible MXene/polydopamine (PDA)-composite-film-based pressure sensor in a portable/wearable fashion, which establishes a unique intercalated spherical-like PDA molecules structure, thereby resulting in excellent sensing performance. The MXene/PDA-based pressure sensor has sensitivity of up to 138.8 kPa-1 in the pressure range of 0.18-6.20 kPa with fast response and recovery speed (t1<100 ms; t2<50 ms). Associated embodiment involves real-time precise measurements of a variety of health-related physiological signals, ranging from wrist pulse, to finger motions, to vocalization and to facial expressions, with high sensitivity and accuracy. Studies on human subjects establish the clinical significance of these devices for future opportunities of health monitoring and intelligent control to predict and diagnose diseases.
Cuproptosis, the current form of regulated cell death characterized by copper overload, oligomerization of lipoacylated proteins, and loss of the Fe-S cluster proteins, has been proposed to function closely with human diseases including cancer. Since the first identification in 2022, a wide range of strategies have been developed to induce cuproptosis for cancer therapy, such as small-molecule drugs and nanomaterials. Although many reviews related to cuproptosis have been reported, they remain at a basic mechanism level and a summary covering recent progress in the field of nanotechnologies in cuproptosis-based cancer therapy has not yet been presented. Therefore, it is time to fill the gap and shed light on future directions for the application of this promising tool to fight against cancer. In this minireview, we first expounded the mechanism of action of cuproptosis and emphasized the feasibility of triggering cuproptosis for cancer therapy. The recent progress of cancer treatments based on nanoparticle-induced cuproptosis was then described. Finally, the challenges and future development directions of the emerging field of cuproptosis were also discussed.