High-performance pyrite nano-catalyst driven photothermal/chemodynamic synergistic therapy for Osteosarcoma.

Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis, and dreadful mortality. Chemotherapy is a commonly used approach for OS treatment but is limited by the development of drug resistance and long-term adverse effects. To date, OS still lacks the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS2@CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS2@CP NPs showed superior Fenton reaction catalytic activity. FeS2@CP NPs-based CDT efficaciously eradicated the tumor cells by initiating dual-effect of killing of apoptosis and ferroptosis. Furthermore, the generated heat from FeS2@CP under near-infrared region II (NIR-II) laser irradiation could not only inhibit tumor's growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy showed excellent osteosarcoma treatment effects both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.

NIR-II Excitable Water-Dispersible Two-Dimensional Conjugated Polymer Nanoplates for In Vivo Two-Photon Luminescence Bioimaging.

While two-dimensional conjugated polymers (2DCPs) have shown great promise in two-photon luminescence (TPL) bioimaging, 2DCP-based TPL imaging agents that can be excited in the second near-infrared window (NIR-II) have rarely been reported so far. Herein, we report two 2DCPs including 2DCP1 and 2DCP2, with octupolar olefin-linked structures for NIR-II-excited bioimaging. The 2DCPs are customized with the fully conjugated donor-acceptor (D-A) linkage and aggregation-induced emission (AIE) active building blocks, leading to good two-photon absorption into the NIR-II window with a 2PACS of ∼64.0 GM per choromophore for both 2DCPs. Moreover, 2DCP1 powders can be exfoliated into water-dispersible nanoplates with a Pluronic F-127 surfactant-assisted temperature-swing method, accompanied by both a drastic reduction of 2PACS throughout the range of 780-1080 nm and a sharp increase of photoluminescence quantum yield to 33.3%. The 2DCP1 nanoplates are subsequently proven to be capable of assisting in visualizing mouse brain vasculatures with a penetration depth of 421 µm and good contrast in vivo, albeit that only 19% of previous 2PACS at 1040 nm is preserved. This work not only provides important insights on how to construct NIR-II excitable 2DCPs for TPL bioimaging but also how to investigate the exfoliation-photophysical property correlation of 2DCPs, which should aid in future research on developing highly efficient TPL bioimaging agents.

Continuous operation of nano-catalytic ozonation using membrane separation coupling system: Influence factors and mechanism.

The application of nano-catalysts in improving the ozonation removal efficiency for refractory organic compounds has been extensively investigated. However, cost-effective nano-catalysts separation remains a challenge. In this study, membrane separation processes were employed to separate nano-MgO catalysts from an ozonation system. A continuous nano-catalytic ozonation membrane separation (nCOMS) coupling system was successfully constructed for treating quinoline. The results showed that long hydraulic retention time (HRT) and high nano-MgO dosage could improve the quinolone removal efficiency but shorten operation cycles. At the optimal operation conditions of HRT = 4 h and nano-MgO dosage = 0.2 g/L, the nCOMS system achieved a stable quinoline removal efficiency of 85.2% for 240 min running with a transmembrane pressure lower than 10 kPa. The quinoline removal efficiency contribution for ozonation, catalysis and membrane separation was 57.1%, 24.9% and 18.0%, respectively. Compared to ozonation membrane separation system, the fouling rate index of the nCOMS system increased by 60% under optimal conditions, but the irreversible fouling was reduced to 28%. In addition, the nCOMS system exhibited reduced adverse effects of coexisting natural organic matter (NOM) on quinoline removal and membrane fouling. In conclusion, the nCOMS system demonstrated higher quinoline removal efficiency, lower irreversible fouling, and reduced adverse effect of coexisting NOM, thereby signifying its potential for practical applications in advanced treatment of industrial wastewater.

Formation and toxicity contribution of chlorinated and dechlorinated halobenzoquinones from dichlorophenols after ozonation.

Halobenzoquinones (HBQs) are a class of disinfection byproducts with high cytotoxicity and potential carcinogenicity, which have been widely detected in chlorination of drinking water and swimming pool water. However, to date, the formation of HBQs upon ozonation and the HBQ precursors have been overlooked. This study investigated the formation of chlorinated and dechlorinated HBQs from six dichlorophenol (DCP) isomers. The monomeric and dimeric HBQs were identified in all the ozonation effluents, exhibiting 1-100 times higher toxicity levels than their precursors. The sum of detected HBQs intensity had a satisfactory linear relation with the maximum toxic unit (R2 = 0.9657), indicating the primary toxicity contribution to the increased overall toxicity of effluents. Based on density functional theory calculations, when ozone attacks the para carbon to the hydroxyl group of 2,3-DCP, the probability of producing chlorinated HBQs is 80.41 %, indicating that the para carbon attack mainly resulted in the formation of monomeric HBQs. 2,3-dichlorophenoxy radicals were successfully detected in ozonated 2,3-DCP effluent through electron paramagnetic resonance and further validated using theoretical calculation, revealing the formation pathway of dimeric HBQs. The results indicate that chlorinated phenols, regardless of the positions of chlorine substitution, can potentially serve as precursors for both chlorinated and dechlorinated HBQs formation during ozonation.

Conjugated Oligoelectrolyte with DNA Affinity for Enhanced Nuclear Imaging and Precise DNA Quantification.

Precise DNA quantification and nuclear imaging are pivotal for clinical testing, pathological diagnosis, and drug development. The detection and localization of mitochondrial DNA serve as crucial indicators of cellular health. We introduce a novel conjugated oligoelectrolyte (COE) molecule, COE-S3, featuring a planar backbone composed of three benzene rings and terminal side chains. This unique amphiphilic structure endows COE-S3 with exceptional water solubility, a high quantum yield of 0.79, and a significant fluorescence Stokes shift (λex = 366 nm, λem = 476 nm), alongside a specific fluorescence response to DNA. The fluorescence intensity correlates proportionally with DNA concentration. COE-S3 interacts with double-stranded DNA (dsDNA) through an intercalation binding mode, exhibiting a binding constant (K) of 1.32 × 106 M-1. Its amphiphilic nature and strong DNA affinity facilitate its localization within mitochondria in living cells and nuclei in apoptotic cells. Remarkably, within 30 min of COE-S3 staining, cell vitality can be discerned through real-time nuclear fluorescence imaging of apoptotic cells. COE-S3's high DNA selectivity enables quantitative intracellular DNA analysis, providing insights into cell proliferation, differentiation, and growth. Our findings underscore COE-S3, with its strategically designed, shortened planar backbone, as a promising intercalative probe for DNA quantification and nuclear imaging.

AIEgens-enhanced rapid sensitive immunofluorescent assay for SARS-CoV-2 with digital microfluidics.

BACKGROUND: Sensitive and rapid antigen detection is critical for the diagnosis and treatment of infectious diseases, but conventional ELISAs including chemiluminescence-based assays are limited in sensitivity and require many operation steps. Fluorescence immunoassays are fast and convenient but often show limited sensitivity and dynamic range. RESULTS: To address the need, an aggregation-induced emission fluorgens (AIEgens) enhanced immunofluorescent assay with beads-based quantification on the digital microfluidic (DMF) platform was developed. Portable DMF devices and chips with small electrodes were fabricated, capable of manipulating droplets within 100 nL and boosting the reaction efficiency. AIEgen nanoparticles (NPs) with high fluorescence and photostability were synthesized to enhance the test sensitivity and detection range. The integration of AIEgen probes, transparent DMF chip design, and the large magnetic beads (10 µm) as capture agents enabled rapid and direct image-taking and signal calculation of the test result. The performance of this platform was demonstrated by point-of-care quantification of SARS-CoV-2 nucleocapsid (N) protein. Within 25 min, a limit of detection of 5.08 pg mL-1 and a limit of quantification of 8.91 pg mL-1 can be achieved using <1 µL sample. The system showed high reproducibility across the wide dynamic range (10-105 pg mL-1), with the coefficient of variance ranging from 2.6% to 9.8%. SIGNIFICANCE: This rapid, sensitive AIEgens-enhanced immunofluorescent assay on the DMF platform showed simplified reaction steps and improved performance, providing insight into the small-volume point-of-care testing of different biomarkers in research and clinical applications.

Comparison of the penetration depth in mouse brain in vivo through 3PF imaging using AIE nanoparticle labeling and THG imaging within the 1700 nm window.

3-Photon microscopy (3PM) excited at the 1700 nm window features a smaller tissue attenuation and hence a larger penetration depth in brain imaging compared with other excitation wavelengths in vivo. While the comparison of the penetration depth quantified by effective attenuation length le with other excitation wavelengths have been extensively investigated, comparison within the 1700 nm window has never been demonstrated. This is mainly due to the lack of a proper excitation laser source and characterization of the in vivo emission properties of fluorescent labels within this window. Herein, we demonstrate detailed measurements and comparison of le through the 3-photon imaging of the mouse brain in vivo, at different excitation wavelengths (1600 nm, 1700 nm, and 1800 nm). 3PF imaging and in vivo spectrum measurements were performed using AIE nanoparticle labeling. Our results show that le derived from both 3PF imaging and THG imaging is the largest at 1700 nm, indicating that it enables the deepest penetration in brain imaging in vivo.

Recent Advances in Engineering Carriers for siRNA Delivery.

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.

Interstitial Optical Fiber-Mediated Multimodal Phototheranostics Based on an Aggregation-Induced NIR-II Emission Luminogen for Orthotopic Breast Cancer Treatment.

One-for-all phototheranostics based on a single molecule is recognized as a convenient approach for cancer treatment, whose efficacy relies on precise lesion localization through multimodal imaging, coupled with the efficient exertion of phototherapy. To unleash the full potential of phototheranostics, advancement in both phototheranostic agents and light delivery methods is essential. Herein, an integrated strategy combining a versatile molecule featuring aggregation-induced emission, namely tBuTTBD, with a modified optical fiber to realize comprehensive tumor diagnosis and "inside-out" irradiation in the orthotopic breast tumor, is proposed for the first time. Attributed to the intense donor-acceptor interaction, highly distorted conformation, abundant molecular rotors, and loose intermolecular packing upon aggregation, tBuTTBD can synchronously undergo second near-infrared (NIR-II) fluorescence emission, photothermal and photodynamic generation under laser irradiation, contributing to a trimodal NIR-II fluorescence-photoacoustic (PA)-photothermal imaging-guided phototherapy. The tumor treatment is further carried out following the insertion of a modified optical fiber, which is fabricated by splicing a flat-end fiber with an air-core fiber. This configuration aims to enable effective in situ phototherapy by maximizing energy utilization for therapeutic benefits. This work not only enriches the palette of NIR-II phototheranostic agents but also provides valuable insight for exploring an integrated phototheranostic protocol for practical cancer treatment.