Latest ArticlesDopamine, a pivotal excitatory neurotransmitter, plays a crucial role in metabolic, cardiovascular, renal, central nervous, and endocrine systems. Abnormal dopamine within the human body can cause various diseases. Therefore, the precise quantification of dopamine levels, both in vivo and in vitro, holds paramount significance for clinical applications and physiological investigations. Carbon dots (CDs) exhibit a plethora of remarkable properties, including a substantial specific surface area, robust electrical conductivity, commendable biocompatibility, minimal toxicity, and high photostability. Considering these unique characteristics, CDs demonstrate substantial potential for fluorescent sensors, colorimetric sensors, and electrochemical sensors for dopamine detection. This review systematically examined the challenges and prospects for the utilization of CDs-based fluorescent sensors, electrochemical biosensors, and colorimetric sensors for monitoring dopamine levels in recent years. These findings unveil promising avenues for further advancements in the field of dopamine detection.
A copper-catalyzed three-component reaction involving cyclic carbonates, elemental sulfur, and H-phosphonates is presented. It proceeds with excellent yields and provides an attractive approach for the construction of valuable trisubstituted allenyl phosphorothioates using a one-step strategy. Moreover, this method can be easily adapted to large-scale preparation.
Patients with oral squamous cell carcinoma (OSCC) encounter challenges in achieving efficient antitumor immunity, primarily due to the inherent pathophysiological characteristics of solid tumors affecting drug accumulation and penetration. Insufficient T-cells and immune escape induced by tumor-associated macrophages (TAMs) further exacerbate these issues. This study utilized M1 macrophage membrane-modified spatial dimension conversion drug delivery systems (SDDDSs) and introduced photosensitizers chlorophyll Pyro and the immune agonist R848. This innovative approach enhanced tumor targeting and accumulation by transforming stimulus-responsive size-reductive SDDDSs into smaller-sized iRGD-Pyro and R848 within the extracellular tumor microenvironment (TME). This facilitated effective drug penetration into deep tumor regions and cellular uptake. The synergistic treatment strategy for OSCC, combining photodynamic therapy (PDT) and tumor immunotherapy, induced tumor cell apoptosis, triggered immunogenic cell death (ICD), polarized TAMs towards the M1 phenotype, promoted sufficient T-cell infiltration, and resulted in significant therapeutic outcomes. This approach offers a promising avenue for future OSCC therapeutic interventions.
Achieving selectivity in cell penetrating peptide (CPP) design is crucial to mitigate systemic toxicity and enable precise targeting based on distinct cellular phenotypes. Herein, we designed an amphiphilic peptide, L17Yp, by incorporating phosphorylated tyrosine into natural occurring M-lycotoxin peptide, known for its potent membrane-lytic activity. This strategic modification induced a conformational shift, as confirmed by circular dichroism spectroscopy, transitioning it from its bioactive α-helix conformation to an inactive random coli configuration, effectively shielding its membrane-penetrating capacity. Upon exposure to alkaline phosphatase, L17Yp undergoes enzymatic dephosphorylation, prompting a conformational shift that restores its membrane-transduction capabilities. This unique property hold promises for selective drug delivery. This work introduces an enzymatic approach for targeted perturbation of the cell membrane, offering promising prospects for precise drug delivery applications.
Photodynamic therapy (PDT) is a promising cancer treatment modality owing to its high spatiotemporal selectivity and noninvasive nature. However, conventional photosensitizers (PSs) used in PDT are responsive only to visible light, which makes them unsuitable for tissue penetration. In this study, we propose a PS based on hot band absorption (HBA), which can be triggered by anti-Stokes light at 808 nm via a one-photon process. The introduction of selenium (Se) into pentamethine cyanine (Secy5) not only facilitates intersystem crossing for reactive oxygen species (ROS) production but also enhances HBA efficiency, thereby prolonging the excitation wavelength. In addition, Secy5 demonstrates excellent biocompatibility, unlike its I-substituted counterpart (Icy5), and produces not only 1O2 but also O2•−, making it a desirable candidate for treating hypoxic solid tumors. According to the results of in vivo and in vitro experiments, Secy5 can efficiently inhibit cancer cell growth via anti-Stokes activation processes, thereby providing a novel approach to design anti-Stokes excitation PSs for anticancer treatment.
Radiotherapy (RT) is a widely used cancer treatment, and the use of metal-based nano-radiotherapy sensitizers has shown promise in enhancing its efficacy. However, efficient accumulation and deep penetration of these sensitizers within tumors remain challenging. In this study, we present the development of bismuth/manganese biomineralized nanoparticles (BiMn/BSA) with multiple radiosensitizing mechanisms, including high atomic number element-mediated radiation capture, catalase-mimic oxygenation, and activation of the stimulator of interferon genes (STING) pathway. Significantly, we demonstrate that low-dose RT induces the recruitment of macrophages and subsequent upregulation of Matrix metalloproteinases (MMP)-2 and MMP-9 that degrade the extracellular matrix (ECM). This dynamic process facilitates the targeted delivery and deep penetration of BiMn/BSA nanoparticles within tumors, thereby enhancing the effectiveness of RT. By combining low-dose RT with BiMn/BSA nanoparticles, we achieved complete suppression of tumor growth in mice with excellent biocompatibility. This study provides a novel and clinically relevant strategy for targeted nanoparticle delivery to tumors, and establishes a safe and effective sequential radiotherapy approach for cancer treatment. These findings hold great promise for improving the outcomes of RT and advancing the field of nanomedicine in cancer therapy.
Deoxyribozyme (DNAzyme) and its substrate hybridization are crucial for achieving desirable detection performance in the DNAzyme coupling nanomaterial biosensor system. However, interfacial factors such as electrostatic repulsion, steric hindrance, and nonspecific adsorption from gold nanoparticles make this hybridization process complicated and challenging. Moreover, the DNAzyme structure changes with different application purposes, which might affect the DNAzyme and substrate’s connection. Few studies have focused on the interplay of DNAzyme and interfacial factors in the biosensor field. In this work, three types of DNAzyme variants were designed, and their biosensor performance rules were studied and summarized with the synergistic effect of interfacial factors. Additionally, corresponding biosensor applications, such as multiple modulation functions and miRNA detections, were constructed based on the distinct principles of DNAzyme variants.
Sonodynamic therapy (SDT) exhibits noninvasive and accuracy in cancer treatment, and has aroused widespread attention. However, the low quantum yield of inorganic sonosensitizers under ultrasound (US) stimulation leads to unsatisfactory efficacy. In this work, an urchin-like piezoelectric ZnSnO3/Cu3P p-n heterojunction was constructed as an efficient sonosensitizer for enhanced SDT. The p-n heterojunction formation narrows the band bandgap and increases the piezoelectric property, which contribute to the promotion of carrier separation and suppression of carrier recombination, resulting in enhanced SDT. Moreover, under tumor microenvironment (TME) with over produced H2O2 and glutathione (GSH), Cu3P NNs induce chemodynamic therapy (CDT) by initiating a Fenton-like reaction and depleting GSH, leading to increased cellular oxidative damage. With the combination effect, the ZnSnO3/Cu3P heterojunction demonstrates a 70% tumor growth inhibition rate in 4T1 tumor mice model. This piezoelectric heterojunction achieves the combined treatment of SDT and CDT, and opens new possibilities for the application of SDT in tumor therapy.
Multimodal bioorthogonal small molecule probes play a pivotal role in drug-focused biomedical research. However, existing drug tracking and imaging techniques face obstacles in living organisms, hindering precise drug localization and target protein capture. Herein, we introduced a multimodal probe named 1-(azidomethyl)pyrene-4,5–dione (AMPD). The probe incorporates adjacent dione structures at the pyrene core. AMPD selectively interacts with oxygen-rich alkene-labeled drug molecules under ice-blue LED light exposure, producing specific fluorescence emission and enabling in vivo tracking and flow cytometry sorting. A methyl azide group was also introduced at the pyrene core to help efficiently enrich target proteins via click chemistry with alkyne-functionalized beads. AMPD demonstrates exceptional biocompatibility, rendering it highly suitable for visual photo-triggered tracking studies. Combined with metabolic labeling using an oxygen-rich alkene-tagged drug molecule probe, AMPD is effective for live animal, tissue, cellular, and in-gel imaging, as well as target protein identification through magnetic capture. With its versatile capabilities, AMPD enhances our comprehension of drug-target interactions at the in vivo level and expedites the process of drug discovery.
The combination of diagnostic and therapeutic agents in the form of theranostic platforms to enhance tumor therapeutic efficacy is receiving increasing attention in recent years. However, simultaneous encapsulation, embedding or conjugation of various agents to traditional theranostic nanocarriers always require intricate synthetic process. Herein, a supramolecular drug-drug self-delivery nanosystem (DSDN) based on a newly developed aggregation-induced emission (AIE) photosensitizer (CBTM) and an anti-tumor tyroservaltide (YSV) was constructed for near-infrared (NIR) fluorescence imaging-guided photodynamic/chemotherapy of tumor. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that YSV and CBTM could co-assemble into YSV/CBTM nanoparticles, with regular round-shape morphology and homogeneous size. Inspiringly, YSV/CBTM nanoparticles could effectively overcome the aggregation-caused quenching (ACQ) effect, and enter CT26 tumor cells with a high NIR fluorescence emission, allowing preoperative diagnosis. Meanwhile, the as-prepared YSV/CBTM could efficiently generate reactive oxygen species (ROS) under NIR light irradiation, exhibiting photodynamic ablation of tumor cells. More importantly, the peptide drug of YSV not only improved the availability of CBTM nanoparticles, but also served as a toxic adjuvant to enhance the photodynamic therapy (PDT) efficacy of CBTM. In vitro and in vivo assays revealed that most of colorectal tumor cells and tumor tissues were thoroughly ablated by photodynamic-chemotherapy integrated nanoparticles, resulting in longer survival of tumor-bearing mice. Regarding the advantages of the YSV/CBTM nanosystem, we believe this research could offer valuable guidance for the design of nanodrugs with high performance for cancer theranostics.
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