Latest ArticlesFocused on the performance promotion of organic small molecular dyes based photothermal agents via non-chemical modification, we found that heat-assisted binding of human serum albumin (HSA) to the dye causes shrinkage of the protein and encapsulate the dye to form nanoparticles. This revolutionizes the photostability of small molecule dyes which further improves their photothermal conversion efficiency and tumor ablation performance as photothermal agents significantly. In this work, the obtained photothermal agent named HSA-P2-T could accumulate in tumor and induce 22 ℃ enhancement of the tumor in xenograft models upon ultra-low dose (0.1 W/cm2) laser irradiation, which, as far as we know, is the lowest laser dose used in vivo photothermal therapy. Utilizing HSA-P2-T, we realized tumor ablation upon twice intravenous injections of the nanoparticles and four photothermal treatments.
Radiotherapy (RT) is a crucial treatment for cancer; however, its effectiveness is limited by adverse effects on normal tissues, radioresistance, and tumor recurrence. To overcome these challenges, hydrogels have been employed for delivery of radiosensitizers and other therapeutic agents. This review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer treatment. Firstly, we introduce the classification and properties of hydrogels. Next, we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and brachytherapy. We also discuss hydrogels used in combination therapy involving RT and immunotherapy. Lastly, we highlight the challenges that hydrogels face in RT. By surveying the latest developments in hydrogel applications for RT, this review aims to provide insights into the development of more effective and targeted cancer therapies.
Here, we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity, thereby facilitating the discovery and optimization of biocompatible reactions. Using this platform, we achieve a Horner-Wadsworth-Emmons (HWE) reaction under physiological conditions, generating a fluorophore in situ with a yield of up to 93%. This proximity platform should facilitate the discovery of various types of biocompatible reactions, making it a versatile tool for biomedical applications.
Cyclooctatetraene (COT) attachment to fluorophores (“self-healing” dyes) is known for quenching reactive triplet states via triplet-state energy transfer (TET), enhancing photostability. However, COT’s impact on singlet states remains unclear. Quantum calculations reveal that COT induces energy transfer to dark states in deep blue dyes while promoting photoinduced electron transfer (PET) and intersystem crossing (ISC) in visible dyes, potentially compromising brightness and/or photostability. To address this, we propose the use of ΔE descriptor to optimize COT’s effects. Our findings uncover COT’s multifaceted impact. These insights will guide the development of superior triplet state quenchers and photostable dyes.
Recently, the utilization of nonsteroidal anti-inflammatory drugs (NSAIDs) to sensitize cisplatin (CDDP) has gained substantial traction in the treatment of ovarian cancer (OC). However, even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events, notably thrombosis. Furthermore, the diminished sensitivity to CDDP therapy in OC is multifactorial, rendering the application of NSAIDs only partially effective due to their cyclooxygenase-2 (COX-2) inhibiting mechanism. Hence, in this study, reactive oxygen species (ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(Ⅳ) prodrug (DTP@AP NPs) were prepared to achieve comprehensive chemosensitization. On one front, allicin achieved COX-2 blocking therapy, encompassing the inhibition of proliferation, angiogenesis and endothelial mesenchymal transition (EMT), thereby mitigating the adverse impacts of CDDP chemotherapy. Simultaneously, synergistic chemosensitization was achieved from multifaceted mechanisms by decreasing CDDP inactivation, damaging mitochondria and inhibiting DNA repair. In essence, these findings provided an optimized approach for synergizing CDDP with COX-2 inhibitors, offering a promising avenue for enhancing OC treatment outcomes.
Fe(II) is an essential trace element for anaerobic ammonium oxidation bacteria (AAOB) metabolism, and can improve the nitrogen removal efficiency of anaerobic ammonia oxidation (Anammox). Here we operated two identical expanded granular sludge bed (EGSB) reactors at low temperature (15 ± 3 ℃) for 154 days. Reactor 1 (R1) received additional Fe(II) (0.12 mmol/L) during the late startup phase, while reactor 0 (R0) served as the control and did not receive extra Fe(II). Nitrogen removal in R1 became stable at 55 d of operation, ten days earlier than R0. The nitrogen removal rate (NRR) of R1 was 1.64 kg N m−3 d−1 and its TN removal rate was as high as 89%, while R0 only reached 75%. The addition of Fe(II) was further beneficial to aggregation and stability of the granular sludge, and the used sludge of both reactors showed enrichment for AAOB populations compared to the inoculum, for instance, increased abundance of Candidatus-Kuenenia and in particular of Candidatus-Brocadia (from 0.17% to 10.10% in R0 and 7.79% in R1). Diverse microbial species and complex microbial network structure in R1 compared to R0 promoted the coupled denitrogenation by Anammox, dissimilatory nitrate reduction to ammonium (DNRA), nitrate-dependent Fe oxidation (NDFO), and ferric ammonium oxidation (Feammox). In addition, the microbial community in R1 was more resistant to short-term low temperature (2–7 ℃) starvation, illustrating a further positive effect of adding Fe(II) during the startup phase of an Anammox reactor.
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal lung disease characterized by pulmonary inflammation, oxidative stress, and excessive extracellular matrix (ECM) deposition. Current anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy, highlighting the urgent necessity for a novel therapeutic strategy. Taraxasterol (TA), which has biological activities against lung injury induced by various factors, is a potential anti-IPF drug due to its anti-inflammatory, antioxidant and lung-protective effects. However, the protective effect of TA on IPF has not been confirmed, and its clinical application is limited due to its poor aqueous solubility. In this study, we demonstrated that TA could inhibit epithelial-mesenchymal transition (EMT) and migration of A549 cells by inhibiting the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. To improve the aqueous solubility and pulmonary administration performance of TA, we prepared TA loaded methoxy poly(ethylene glycol)-poly(d, l-lactide) (mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate (TPGS) mixed polymeric micelles (TA-PM). Then a MicroSprayerⓇ Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin (BLM)-induced IPF mice. Our results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation, oxidative stress and fibrosis in lung tissue. Furthermore, TA-PM exhibited high pulmonary deposition and retention by pulmonary administration, along with a favorable safety profile. Overall, this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF, providing a new opportunity for their clinical application.
The concentration of metallic elements is closely associated with overall health. However, the discharge of untreated industrial wastewater can lead to metal-containing pollutants entering the human body through the food chain, disrupting the organism's homeostasis and posing a risk to human health. Covalent organic framework materials (COFs) have emerged as a novel porous material for detecting or adsorbing metal ions due to their unique pore structure, topological structure and flexible design. This paper summarizes the role, toxicity, and sources of metal ions related to human health, as well as the design, synthesis and performance of COFs fluorescent materials for detecting these elements. The interaction mechanism of different fluorescent COFs and metal ions are discussed. Additionally, the remaining challenges and prospects of COFs fluorescence sensors are provided. We believe this review will be useful in directing the development of fluorescent COFs towards metal ions.
The selective 2e− ORR reaction on polymeric carbon nitride framework is one of the most promising approaches for solar-driven hydrogen peroxide production. Poly(heptazine imide) (PHI) as a class of K+-incorporated crystalline carbon nitride framework, is highly active for photocatalytic H2O2 production. An upgrade on the H2O2 photoproduction performance of PHI is realized and the mechanistic insights are revealed in this work. By photochemical reaction, the electron withdrawing groups of hydroxyl group and cyano group are grafted on the surface of PHI frameworks. The dual polarization sites on the surface contribute significantly to the enhancement of the exciton dissociation. The optimized PHI with dual polarization sites exhibits a remarkable photocatalytic H2O2 production performance, which is 2 times of the active pristine PHI. Most importantly, the photochemical reaction method is generally applicable to improve the exciton dissociation of a wide range of polymeric carbon nitride frameworks with various structure and compositions; and the thiourea-derived polymeric carbon nitride framework with dual surface polarization sites exhibits a remarkable photocatalytic performance with a high H2O2 production rate of 40.5 mmol h−1 g−1.
Oxidative therapies receive a limited antitumor efficiency due to the insufficient reactive oxygen species (ROS) levels at focal sites and the evolvement of antioxidant defense systems. Herein, we develop an albumin-based nanomedicine to co-deliver chlorin e6 (Ce6) and COH-SR4 (CS), which can simultaneously enhance the yield and lethality of intracellular ROS for amplified photodynamic therapy (PDT). In which, CS acts as both an activator of AMP-activated protein kinase (AMPK) and an inhibitor of glutathione S-transferases (GSTs). Benefiting from it, the prepared HSA-Ce6@COH-SR4 (HCCS) enables positive feedback uptake by promoting AMPK phosphorylation, leading to rapid and extensive tumor accumulation of drugs. As a result, HCCS obviously increases the ROS production to elevate intracellular oxidative stress. Furthermore, HCCS can inhibit GSTs to disturb the antioxidant defense system of tumor cells, intensifying the oxidative damage of ROS. Ultimately, the PDT of HCCS is significantly strengthened by improving the ROS yield and lethality, which greatly declines the proliferation of breast cancer in vivo. This study may open a window in the development of drug co-delivery system for enhanced oxidative therapy of tumors.
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