Latest ArticlesPhotodynamic 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.
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.
2-Deoxy-α-C-Glycosides are a significant class of carbohydrates found in numerous bioactive molecules and medicines. Developing a concise strategy for the assembly of these α-configured C-glycosides is crucial in the field of carbohydrate chemistry. However, current methods are restricted to the utilization of glycosyl radical precursors, which are required for pre-syntheses. Herein, we present a novel approach for the synthesis of 2-deoxy-α-C-glycosides using a nickel-catalyzed stereoselective coupling reaction with commercially available glycals. Notably, this method circumvents the preparation for diverse glycosyl radical precursors. The developed protocol exhibits a broad substrate scope and remarkable stereoselectivity under mild reaction conditions. Furthermore, the raw materials required for this process are readily accessible, eliminating the necessity for pre-functionalization modifications of the glycosyl substrates and ensuring high atomic economy.
Dopamine, 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.
To address the pressing global need for carbon-neutral fuels, optimizing the conversion of biomass to bio-oil (bio-chemicals) is crucial. Here, we introduce MXene (Ti3C2Tx) as an innovative catalyst in biomass pyrolysis, exhibiting significant prowess in boosting levoglucosan yields. Py-GC/MS analysis indicated a remarkable 438% enhancement in levoglucosan yield when a 5 wt% catalyst-to-biomass ratio was employed. Laboratory-scale studies achieved an impressive 13.95 wt% levoglucosan in ex-situ fixed-bed catalytic pyrolysis, a yield that is 19.6 times higher than that from pure biomass at 40 wt% catalyst loading. Recycling evaluations affirm the robust stability of the MXene catalyst, validating its potential for multiple use cycles in eco-friendly industrial levoglucosan production.
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.
Colorectal cancer is a common cancer worldwide. Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity, which can lead to adverse side effects and limited therapeutic efficacy. In this study, a library of one kind of biodegradable and biocompatible polymer, leucine based-poly(ester amide)s (Leu-PEAs) was developed and utilized as drug carrier. The structure of Leu-PEAs can be tuned to alter their physicochemical properties, enhancing drug loading capacity and delivery efficiency. Leu-PEAs can self-assemble into nanoparticles by nanoprecipitation and load paclitaxel (PTX) with the diameter of ~108 nm and PTX loading capacity of ~8.5%. PTX-loaded Leu-PEAs nanoparticles (PTX@Leu-PEAs) demonstrated significant inhibition of CT26 cell growth in vitro. In vivo, these nanoparticles exhibited prolonged tumor accumulation and antitumor effects, with no observed toxicity to normal organs. Furthermore, blank Leu-PEAs nanoparticles also showed antitumor effects in vitro and in vivo, which may be attributed to the activation of the mammalian target of rapamycin (mTOR) pathway by leucine. Consequently, this biocompatible Leu-PEAs nano-drug delivery system shows potential as a promising strategy for colorectal cancer treatment, warranting further investigation.
The prodrug strategy provides an opportunity for improving the therapeutic index of drugs and avoiding their side effects. The main challenge lies in the fast and effective release of the parent drugs at the desired site under specific stimuli. Herein, a cooperative prodrug activation approach with exogenous native enzyme and endogenous tumor small molecule biomarkers was developed. Chemically, precursors of methylene blue (MB) and resorufin (RSF) react with horseradish peroxidase (HRP)/hydrogen peroxide (H2O2) to quickly and quantitatively release parent dyes and drugs containing amines or carboxylic acids. The application of this approach in mammalian cells was demonstrated with cooperative-activated photodynamic therapy based on a precursor of MB. Compared with free MB, much higher selectivity toward cancer cells was achieved with this approach as evaluated by the selectivity index (SI). This study provides a new method for fast and effective targeted prodrug activation with no need for antibody modification compared with traditional enzyme/prodrug therapy.
In polarized cells, the differential distribution of proteins results in the formation of apical and basolateral membranes. The basolateral membrane contacts basal lamina and mediates cell-to-cell communication, which is crucial for maintaining homeostasis and enabling drug absorption. To establish and maintain the basolateral domain, intricate mechanisms are necessary to ensure the proper sorting and transportation of molecules. Sorting signals play a crucial role in regulating the distributions of basolateral proteins, determining their trafficking route and final residence. Newly synthesized proteins can be segregated into different carrier vesicles at either trans-Golgi network (TGN) or endosomes. Additionally, understanding basolateral transport in polarized epithelial cells is important for predicting diseases and delivering drugs. This review provides a summary of recent advancements in the mechanisms and applications of basolateral sorting and trafficking.
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