Latest ArticlesProteolysis-targeting chimera (PROTAC) has emerged as an efficient strategy to accurately control intracellular protein levels. However, conventional PROTACs are generally limited by nonspecific protein degradation and off-tissue side effects. Particularly, there is a lack of effective chemical tools for visualizing protein degradation. Herein, a near-infrared fluorescent and theranostic PROTAC (PRO-S-DCM) was designed for imaging the degradation of bromodomain-containing protein 4 (BRD4). PRO-S-DCM could be tumor-specifically activated and exhibited favorable imaging effects both in vitro and in vivo. PRO-S-DCM was proven to be a theranostic probe, which potently inhibited growth, invasion and migration of HeLa cells and induced cell apoptosis.
The potential of metal nanoclusters in biomedical applications is limited due to aggregation-caused quenching (ACQ). In this study, an in situ self-assembled pitaya structure was proposed to obtain stable fluorescence emission through protein coronas-controlled distance between gold nanoclusters (Au NCs). Interestingly, the gold ion complexes coated with proteins of low isoelectric point (pI) nucleate at the secondary structure of proteins with high pI through ionic exchange within cells, generating fluorescent Au NCs. It is worth noting that due to the steric hindrance formed by the protein coronas on the surface of Au NCs, the distance between Au NCs can be controlled, avoiding electron transfer caused by close proximity of Au NCs and inhibiting fluorescence ACQ. This strategy can achieve fluorescence imaging of clinical tissue samples without observable side effects. Therefore, this study proposes a distance-controllable self-assembled pitaya structure to provide a new approach for Au NCs with stable fluorescence.
As PEGylated liposomes have witnessed remarkable advancements in drug delivery, their immunogenicity has emerged as a notable challenge. In this study, we discovered that a simple pre-injection of folic acid (FA) effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells. FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells, thereby reducing splenic lymphocyte proliferation and specific IgM secretion. This modulation alleviated IgM-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin. These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.
Bacterial infection, insufficient angiogenesis, and oxidative damage are generally regarded as key issues that impede wound healing, making it necessary to prepare new biomaterials to simultaneously address these problems. In this work, monodispersed CeO2@CuS nanocomposites (NCs) were successfully prepared with tannin (TA) as the reductant and linker. Due to abundant oxygen vacancies in CeO2 and the polyphenolic structure of TA, the TA-CeO2@CuS NCs exhibited a remarkable antioxidant ability to scavenge excessive reactive oxygen species (ROS), which would likely induce serious inflammation. In addition, the TA-CeO2@CuS NCs demonstrated excellent antibacterial capability with near-infrared ray (NIR) irradiation, and the released copper ions could promote the regeneration of blood vessels. These synergistic effects indicated that the synthesized TA-CeO2@CuS NCs could serve as a promising biomaterial for multimodal wound therapy.
Currently, it is still a challenge to develop an organic photosensitizer (PS) with outstanding near-infrared absorption, low O2 dependence, precise tumor targeting and rapid clearance through the kidney to improve the overall outcome of phototherapy. In this study, we have designed an organic PS (NcPB) with an excellent near-infrared light absorption through a refined molecular strategy. Meanwhile, NcPB was assembled into nanoparticles with different sizes (NanoNcPB-1 and NanoNcPB-0) by a supramolecular modulation strategy. As the results, the nanoparticle with an ultra-small size (NanoNcPB-1) generated a large number of superoxide anion (O2•−) in a low-O2-dependent manner and release plenty of heat. Furthermore, the results of in vivo experiments demonstrated that NanoNcPB-1 actively accumulated in tumor tissues and showed a 92% tumor inhibition after photodynamic and photothermal combination therapy. More importantly, NanoNcPB-1 could be rapidly cleared from the body of mice via the renal pathway, which alleviates potential side effects of prolonged retention of PS in the circulation.
Covalent organic frameworks (COFs) are crystalline porous polymeric materials composed of organic monomers connected by strong covalent bonds and offer high stability, good crystallinity, a large specific surface area, and controllable structures. COFs are widely used in the fields of adsorption and separation, catalysis, photovoltaics, and drug-delivery. The structural regulation and performance optimization of COFs can be realized through the modification of ligands and the selection of linkage methods. In which, the types of linkage are closely related to the stability and performance of COFs. In this review, nitrogen-containing linkage-bonds (NCLBs) in COFs are divided into N-containing double bonds, N-containing conjugated rings and N-containing unconjugated rings. The association between structure and performance of COFs is elaborated and the synthesis methods of COFs are systematically summarized. Moreover, the structural design, theoretical prediction and machinable application of COFs are prospected
Receptor tyrosine kinases (RTKs) are biological enzymes expressed on cell membranes that can influence cellular signaling, and their overexpression in tumor cells makes them a key route to assess relevant tumor processes. The development of a delivery system that targets and accumulates in RTKs overexpressing-cells at the on-target site is significant for the monitoring of tumor progression and clinical applications through longer tumor site signaling response under low injection frequency. Here, a host-guest nanoscale fluorescent probe SNI@ZIF-8 based on zeolitic imidazolate framework-8 (ZIF-8) and a fluorescent probe SNI constructed from receptor tyrosine kinase inhibitor was proposed and prepared for targeting RTKs and enabling prolonged fluorescence imaging in vivo. The folded conformation of the probe SNI resulted in low background fluorescence, and the unfolding of the SNI conformation upon insertion of the RTKs active pocket showed significant fluorescence enhancement thus enabling real-time detection of RTKs. The host-guest system SNI@ZIF-8 could release guest molecules due to the presence of the enzyme, emphasizing the reporting of stable fluorescent signals over time under low injection frequency. SNI@ZIF-8 could provide a signal response on the cell membrane of RTKs overexpressing cells without interference from other substances, and provided a longer fluorescent signal than SNI at equivalent number of injections in tumor-bearing mice. The host-guest system SNI@ZIF-8, with its obvious tumor site enrichment ability and clear fluorescence imaging ability, could be successfully applied to the detection of RTKs on cell membranes in biological systems, providing a new strategy for determining the process of tumor development in clinical applications.
Breath analysis can be used to diagnose diseases non-invasively. Accurate measurement of volatolomics is critical for breath analysis to be a gold standard. Tedlar bags (TB) are often used to collect breath samples, but they emit contaminants that affect accuracy. This issue was overlooked in previous studies. We found contamination issues with TB (e.g., siloxanes and aromatic impurities) that affect the identification of volatile organic compounds (VOCs) due to impurities. Then, home-designed equipment (HD) made with poly-tetrafluoride (PTFE) and quartz glass for breath collection was developed and employed in clinical trials. 15 healthy individuals and 32 non-small cell lung cancer (NSCLC) patients at IA stage participated in this study. 610 VOCs can be collected through TB, which is less than HD (1109 VOCs), demonstrating that the inner wall of the TB easily adsorbs VOCs, leading to decreased detection concentrations. Otherwise, utilizing orthogonal partial least squares discriminant analysis (OPLS-DA), we identified chemical markers with significant discriminatory power (VIP > 1.5, P < 0.05). The HD method identified 12 target VOCs, surpassing the 3 target VOCs discerned by the TB method. A model combined with a machine learning algorithm for distinguishing early-stage lung cancer patients was established based on biomarkers, which were selected based on OPLS-DA. The results showed strong predictive capabilities for the HD-based model. It indicated that 12 biomarkers derived from the HD model were more effective in distinguishing NSCLC patients, with an AUC value of 0.92, compared to the AUC value of 0.5 from 3 markers obtained from the TB model. The sensitivity and specificity in the confusion matrix reached 100% and 80% for the HD test, but TB test reached only 40% and 60%. This work demonstrated that optimizing and standardizing VOCs collection methodology from breath of lung cancer patients is essential to identify actual volatiles, which could promote disease volatolomics worldwide.
Electrocatalytic water splitting for hydrogen production is a key approach to tackling the current energy crisis. Among the catalysts, the traditional Pd@C catalysts are remarkable for their efficiency in hydrogen evolution. However, the high cost and scarcity of Pd catalysts, as well as the instability caused by the corrosiveness of carbon-based substrates, hinder their large-scale application. To overcome this challenge, an effective strategy is to construct highly dispersed Pd single atoms to improve palladium utilization and choose more stable materials as supports. In this study, TiO2−x carriers with abundant oxygen vacancies were prepared and loaded with Pd by photoreduction deposition. Adjusting the palladium content resulted in three forms of Pd-loaded TiO2−x: nanoparticles (Pd@TiO2−x(6%, 10%)), nanoclusters (Pd@TiO2−x(3%)) and single atoms (Pd@TiO2−x(1.5%)). The oxygen vacancies improved the stability of the titanium dioxide materials by providing more active hydrogen adsorption sites and increasing the affinity of Pd for active hydrogen. Single atom loading increased the frequency of oxygen holes in the support and the high activity of monatomic Pd promoted the adsorption of active hydrogen and facilitated the formation of active hydrogen intermediates. The synergistic effect of single atoms and oxygen vacancies improved the stability and catalytic activity of the composite material. Pd@TiO2−x(1.5%) showed outstanding performance in hydrogen evolution in an acidic medium with an overpotential of only 24 mV at a current density of 10 mA/cm2 and a low Tafel rise of 41.9 mV/dec. This study provides an effective strategy for the development of high-performance hydrogen evolution (HER) catalysts.
The efficacy of photodynamic therapy (PDT) for breast tumors is hindered by challenges such as inadequate tumor targeting, limited treatment depth, and strong oxygen dependence. Herein, a promising photosensitizer VP-B was developed to simultaneously address all the aforementioned issues for the treatment of hypoxic deep-seated breast tumors. The biotinylated photosensitizer VP-B not only exhibited precise targeting towards breast tumor tissue, but also efficiently triggered the generation of abundant 1O2 and O2−• under 690 nm red light irradiation. Indeed, the red light penetration ability enabled VP-B to achieve successful application in a mouse orthotopic breast tumor model. After intravenous administration, VP-B can selectively target tumor tissues and significantly inhibit the growth of hypoxic deep-seated tumors. Therefore, this new type Ⅰ & Ⅱ photosensitizer could boost fluorescence-guided photodynamic therapy of other hypoxic solid tumors.
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