Engineering H2O2 Self-Supplying Platform for Xdynamic Therapies via Ru-Cu Peroxide Nanocarrier: Tumor Microenvironment-Mediated Synergistic Therapy.

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H2O2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H2O2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuxCu1-xO2-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuxCu1-xO2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (OV) density, which grants them the potential to form massive Lewis's acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H2O2, Ru2+/3+, and Cu+/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (1O2) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic therapeutic effectiveness in vitro and in vivo.

Preclinical Assessment of Enhanced Chemodynamic Therapy by an FeMnOx-Based Nanocarrier: Tumor-Microenvironment-Mediated Fenton Reaction and ROS-Induced Chemotherapeutic for Boosted Antitumor Activity.

In recent studies, iron-containing Fenton nanocatalysts have demonstrated significant promise for clinical use due to their effective antitumor activity and low cytotoxicity. A new approach was reported in this work utilizing cation exchange synthesis to fabricate FeMnOx nanoparticles (NPs) that boost Fenton reactions and responses to the tumor microenvironment (TME) for chemodynamic therapy (CDT) and chemotherapy (CT). Within the TME, the redox metal pair of Fe2+/Mn2+ helps break down endogenous hydrogen peroxide (H2O2) into very harmful hydroxyl radicals (•OH) while simultaneously deactivating glutathione (GSH) to boost CDT performance. To further enhance the therapeutic potential, FeMnOx NPs were encapsulated with thioketal-linked camptothecin (CPT-TK-COOH), a reactive oxygen species (ROS)-responsive prodrug, achieving a high CPT-loading capacity of up to 51.1%. Upon ROS generation through the Fenton reaction, the prodrug TK linkage was disrupted, releasing 80% of the CPT payload within 48 h. Notably, FeMnOx@CPT exhibited excellent dual-modal imaging capabilities, enabling magnetic resonance and fluorescence imaging for image-guided therapy. In vitro studies showed the cytocompatibility of FeMnOx NPs using MDA-Mb-231 and 4T1 cells, but in the presence of H2O2, they induced significant cytotoxicity, resulting in 80% cell death through CDT and CT effects. Upon intravenous administration, FeMnOx@CPT displayed remarkable tumor accumulation, which enhanced tumor suppression in xenografts through improved CDT and CT effects. Moreover, no significant adverse effects were observed in the FeMnOx NP-treated animals. In the current study, the FeMnOx@CPT anticancer platform, with its boosted •OH-producing capability and ROS-cleavable drug release, has been validated utilizing in vitro and animal studies, suggesting its capacity as a viable strategy for clinical trials.

Molybdenum-oxo-sulfide quantum dot-based nanocarrier: Efficient generation of reactive oxygen species via photo/chemodynamic therapy and stimulus-induced drug release.

The fabrication of multifunctional nano-therapies has increased gradually to strengthen the therapeutic performance and minimize adverse effects of traditional cancer treatment strategies. Currently, we have designed a facile preparation drug-loaded nanocarrier for multimodal cancer therapy upon external stimuli. First, defect-rich molybdenum oxo-sulfide (MoOxS2-x) quantum dots (QDs) was synthesized via rapid biomineralization techniques with superior optical quantum yield reaching upto 37.28%. The presence of the Fenton ion, Mo+IV/+VI, enables MoOxS2-x QDs to efficiently catalyze peroxide solutions to produce •OH radicals for chemodynamic treatment (CDT) and also deactivate the intracellular glutathione (GSH) enzymes through redox reaction for boosted reactive oxygen species (ROS)-mediated therapies. In addition, upon laser combination, MoOxS2-x QDs generate ROS for photodynamic therapy (PDT). Also, due to a large amount of sulfide content, MoOxS2-x QDs showed excellent H2S gas release in acidic pH for cancer gas therapy. Then, MoOxS2-x QDs was further conjugated with ROS-responsive thioketal linked Camptothecin (CPT-TK-COOH) drug, forming a multitargeted MoOxS2-xCPT anticancer agent with better drug-loading efficiency (38.8%). After triggering the ROS generation through the CDT and PDT mechanisms, the thioketal linkage was disrupted, releasing up to 79% of the CPT drug in 48 h. Besides, in vitro experiments verified that MoOxS2-x QDs possess higher biocompatibility with 4T1 and HeLa cells but also showed considerable toxicity in the presence of laser/H2O2, resulting in 84.45% cell death through PDT/CDT and chemotherapeutic effects. Therefore, the designed MoOxS2-xCPT exhibited outstanding therapeutic benefits for image-guided cancer therapy.

Multifunctional manganese oxide-based nanocomposite theranostic agent with glucose/light-responsive singlet oxygen generation and dual-modal imaging for cancer treatment.

Development of tumor microenvironment (TME) modifying nanomedicine with cooperative effect between multiple stimuli responsive therapeutic modalities is necessary to achieve lower dosage induced tumor specific therapy. Accordingly, herein, a multifunctional MnOx NSs@BSA-IR780-GOx nanocomposite (MBIG NCs) is developed to modulate the oxidative stress in TME, and thus attain higher therapeutic efficacy. In the presence of glucose, the as-synthesized MBIG NCs are served as a chemodynamic agents and generated reactive oxygen species (ROS) by self-activation through a cascade of reactions from glucose oxidase (GOx) and manganese oxide nanosheets (MnOx NSs). Also, the MBIG NCs demonstrated excellent photodynamic properties upon irradiation with 808 nm laser owing to the presence of IR780. The combination of glucose-mediated chemodynamic and light-mediated photodynamic properties generated higher ROS than that obtained with individual stimuli. Further, the MBIG NCs exhibited photothermal effect with conversion efficiency of 33.8 %, which helped to enhance the enzymatic activities. In in vitro studies, the MBIG NCs exhibited good biocompatibility to cancerous and non-cancerous cells under non-stimulus conditions. Nevertheless, in the presence of glucose and light stimuli, they triggered more than 90 % cell toxicity at 200 ppm concentration via the cooperative effect between starvation therapy, chemodynamic therapy, and phototherapy. Furthermore, the MBIG NCs demonstrated magnetic resonance and fluorescence imaging properties. These results are suggesting that MBIG NCs would be potential theranostic agents to for cancer diagnosis and target specific therapy. More importantly, the fabrication process is paving a way to improve the aqueous dispersibility, stability, and bio-applicability of MnOx NSs and IR780.

Composition, Morphology, and Interface Engineering of 3D Cauliflower-Like Porous Carbon-Wrapped Metal Chalcogenides as Advanced Electrocatalysts for Quantum Dot-Sensitized Solar Cells.

Designing a low-cost, highly efficient, and stable electrocatalyst that can synergistically speed up the reduction of polysulfide electrolytes while operative for long periods in the open air is critical for the practical application of quantum dot-sensitized solar cells (QDSSCs), but it remains a challenging task. Herein, a simple, straightforward, and two-step nanocomposite engineering approach that simultaneously combines metallic copper chalcogenides (MC) either Cu2- x S or Cu2- x Se with S, N dual-doped carbon (SNC) sources for devising high-quality counter electrode (CE) film are reported. First, the hierarchically assembled MC nanostructures are obtained using microwave-assisted synthesis. Second, these MCs are embedded within an ordered macro-meso-microporous carbon matrix to obtain Cu2- x S@C or Cu2- x SeS@C CE. These CEs are demonstrated to have composition dependents crystal structure, surface morphologies, photovoltaic performance, and electrochemical properties. In terms of power conversion efficiency (PCE), the Cu2- x SeS@C (9.89%) and Cu2- x S@C-CE (8.96%) constructed QDSSCs outperform both Cu2- x Se (8.96%) and Cu2- x S-constructed (7.79%) QDSSCs, respectively. The enhanced PCE could be attributed to the synergistic interaction of S and N dopants with MC interfaces that can not only enrich electric conductivity, and a higher surface-to-volume ratio but also offers a 3D network for superior charge transport at the interface.

Engineering the Surface of Ti3C2 MXene Nanosheets for High Stability and Multimodal Anticancer Therapy.

The surface of Ti3C2 MXene nanosheets (TC NSs) was first modified with the antioxidants sodium ascorbate (SA) and dopamine (DA) (DSTC NS) to improve their stability in oxidative and hydration environments and thereby improve their bioapplications. This novel approach not only improved MXene stability by arresting oxidation but also increased the available functional groups for further functionalization with various biomolecules. The DSTC NSs were then sequentially conjugated with enzyme glucose oxidase (GOx) and photosensitizer Ce6 to render the obtained CGDSTC NSs with glucose starvation and photodynamic therapeutic properties and thus attain high efficiency in killing cancer cells through the cooperative effect. The as-synthesized CGDSTC NSs demonstrated tremendous photothermal effect with conversion efficiency of 45.1% and photodynamic (ROS generation) properties upon irradiation with 808 and 671 nm lasers. Furthermore, it was observed that the enzymatic activity of CGDSTC NSs increased upon laser irradiation due to enhanced solution temperature. During in vitro studies, the CGDSTC NSs exhibited cytocompatability to HePG2 and HeLa cells under nonstimulus conditions. However, they elicited more than 90% cell-killing efficiency in the presence of glucose and laser irradiation via the cooperative effect between starvation therapy and phototherapy. These results indicate that CGDSTC NSs could be used as potential therapeutic agents to eradicate cancers with no or few adverse effects. This surface modification approach is also simple and facile to adopt in MXene-based research.

Highly Luminescent, Stable, and Red-Emitting CsMgxPb1-xI3 Quantum Dots for Dual-Modal Imaging-Guided Photodynamic Therapy and Photocatalytic Activity.

In this study, for the first time, red-emitting CsMgxPb1-xI3 quantum dots (QDs) are prepared by doping with magnesium (Mg) ions via the one-pot microwave pyrolysis technique. The X-ray diffraction and X-ray photoelectron spectroscopy results have confirmed partial substitution of Pb2+ by Mg2+ inside the CsPbI3 framework. The as-synthesized CsMgxPb1-xI3 QDs have exhibited excellent morphology, higher quantum yield (upto ∼89%), better photostability and storage stability than undoped CsPbI3. Next, the bioavailability of as-synthesized hydrophobic CsMgxPb1-xI3 QDs is improved by encapsulating them into gadolinium-conjugated pluronic 127 (PF127-Gd) micelles through hydrophobic interactions (PQD@Gd). The optical properties of perovskite quantum dots (PQDs) and the presence of Gd could endow the PQD@Gd with fluorescence imaging, magnetic resonance imaging (MRI), and phototherapeutic properties. Accordingly, the MRI contrasting effects of PQD@Gd nanoagents are demonstrated by employing T1 and T2 studies, which validated that PQD@Gd nanoagents had superior MR contrasting effect with a r2/r1 ratio of 1.38. In vitro MRI and fluorescence imaging analyses have shown that the PQD@Gd nanoagents are internalized into the cancer cells via a caveolae-mediated endocytosis pathway. The PQD@Gd nanoagents have exhibited excellent biocompatibility even at concentrations as high as 450 ppm. Interestingly, the as-prepared PQD@Gd nanoagents have efficiently produced cytotoxic reactive oxygen species in the cancer cells under 671 nm laser illumination and thereby induced cell death. Moreover, the PQD@Gd nanoagent also demonstrated excellent photocatalytic activity toward organic pollutants under visible light irradiation. The organic pollutants rhodamine b, methyl orange, and methylene blue were degraded by 92.11, 89.21, and 76.21%, respectively, under 60, 80, and 100 min, respectively, irradiation time. The plausible mechanism for the photocatalytic activity is also elucidated. Overall, this work proposes a novel strategy to enhance the optical properties, stability, and bioapplicability of PQDs. The multifunctional PQD@Gd nanoagents developed in this study could be the potential choice of components not only for cancer therapy due to dual-modal imaging and photodynamic therapeutic properties but also for organic pollutant or bacterial removal due to excellent photocatalytic properties.