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.

High performance carbon dots based prodrug Platform: Image-Guided photodynamic and chemotherapy with On-Demand drug release upon laser irradiation.

The design of therapeutic nanoplatforms based on fluorescent carbon dots (CDs) has become a viable strategy because of their aqueous solubility, biocompatibility, and ease of further functionalization. By doping various heteroatoms into pristine CDs structures, we synthesized N-, Cl-, and S-doped CDs (NClS/CDs), as well as Se-, N-, and Cl-doped CDs (NClSe/CDs) with superior optoelectronic properties using rapid and straightforward microwave heating. The quantum efficiencies of these NClS/CDs and NClSe/CDs were enhanced to 30.7 % and 42.9 %, respectively, compared to those of undoped CDs (0.66 %). Owing to their better light absorption properties, NClS/CDs efficiently produced reactive oxygen species (ROS) under 532 nm laser irradiation for photodynamic therapy (PDT). Considering the ROS generation and surface carrier abilities of NClS/CDs, we designed the loading of camptothecin (CPT) drug via a thioketal linker (TL), resulting in h/CDs@CPT nanovesicles (NVs) with a drug-loading efficiency of 46.5 %. Under laser irradiation in an acidic environment, ROS-triggered CPT release was observed, with 50.2 % of CPT released following the breakdown of the ROS-sensitive TL. In vitro cellular studies revealed that h/CDs@CPT NVs possessed minimal cytotoxicity toward HeLa and 4 T1 cancer cells, despite the high clinical efficacy of PDT and ROS-induced chemotherapeutic response under laser treatment. Confocal microscopy of HeLa and 4 T1 cells revealed that h/CDs@CPT NVs produced red-emissive photographs for potential cancer cell detection. Therefore, our study presents an image-guided PDT and chemotherapeutic platform based on h/CDs@CPT NVs, which will be an attractive candidate for future cancer treatment.

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.

Brightly luminescent (NH4)xCs1-xPbBr3 quantum dots for in vitro imaging and efficient photothermal ablation therapy.

Herein, we report for the first time a facile strategy for the highly efficient (NH4)xCs1-xPbBr3 quantum dots (QDs). By modulating the amount of ammonium, (NH4)xCs1-xPbBr3 QDs with different photoluminescence (PL) quantum yields (QY) were synthesized. The results of X-ray diffraction and X-ray photoelectron spectroscopy showed that the crystal structure of (NH4)xCs1-xPbBr3 was altered by incorporation of NH4+ cations into the CsPbBr3 lattice. The (NH4)xCs1-xPbBr3 QDs showed enhanced PL QY, higher photostability, and long-term storage stability compared to CsPbBr3 QDs. Furthermore, (NH4)xCs1-xPbBr3 QDs could be conjugated with a photothermal dye (IR780) via a one-pot reaction using poly(styrene-co-maleic anhydride) and IR780-MPTS. To the best of our knowledge, the present work is the first attempt integrating perovskite QDs and phototherapeutic molecules into one system (abbreviated as PQD-IR780), demonstrating good water dispersibility and high photothermal conversion efficiency of 57.85%. In vitro experiments performed to examine subcellular uptake showed high fluorescence brightness was observed in HeLa, B16F1, and HepG2 cancer cells cultured with PQD-IR780. The results indicate that the internalization mechanism for uptaking of PQD-IR780 inside HeLa cells is energy-dependent and caveolin-mediated endocytosis. The in vitro cell viability assays and photothermal therapy revealed that PQD-IR780 showed good biocompatibility and can induce hyperthermia upon laser irradiation.

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.

Efficient quantum dot-sensitized solar cells through sulfur-rich carbon nitride modified electrolytes.

For quantum dot sensitized solar cells (QDSSCs), modifying conservative polysulfide electrolytes with polymer additives has been proven as an effective method to control charge recombination processes at the TiO2/QDs/electrolyte interface and to accomplish efficient cell devices. In this respect, the polysulfide electrolyte is modified with polymeric and sulfur-rich graphitic carbon nitride (SGCN) to enhance the photovoltaic performance of QDSSCs. For the first time, SGCN is used to passivate surface trap states and act as the steric hindrance between TiO2/QDs/electrolyte interfaces. The QDSSCs fabricated with GCN and SGCN additives exhibited higher efficiencies, especially improved short-circuit current (JSC) and fill factors (FFs) than those of the liquid electrolyte. Cu-In-S sensitized QDSSCs constructed with GCN and SGCN additives exhibited efficiencies of 6.73% and 7.13%, respectively, whereas the liquid electrolytes delivered an efficiency of 6.16%. Additionally, the applicability of SGCN additives in various Cu-based QDSSCs to enhance their photovoltaic performance is further verified using Cu-In-Se QDSSCs. An increase in the conversion efficiencies of QDSSCs with SGCN additives is possibly due to (1) their electron-rich surface which can act as an obstacle for electron-hole recombination, thereby suppressing the back-transfer of photo-induced electrons to the QD/electrolyte interface; (2) SGCN facilitates the reduction of Sn2- to S2- redox couple, thus providing holes towards the QDs/electrolyte more efficiently. Overall, this work provides an innovative and economic additive to modify polysulfide electrolytes, thereby controlling the TiO2/QDs/electrolyte interfaces of QDSSCs.

Biomimetic Nanoreactor for Cancer Eradication via Win-Win Cooperation between Starvation/Photo/Chemodynamic Therapies.

Combining phototherapy with the cancer cell metabolic pathway altering strategies, that is, glucose starvation, would be a promising approach to accomplish high curative efficiency of cancer treatment. Accordingly, herein, we sought to construct a multifunctional biomimetic hybrid nanoreactor by fastening nanozyme AuNPs (glucose oxidase activity) and PtNPs (catalase and peroxidase activity) and photosensitizer Indocyanine green (ICG) onto the polydopamine (PDA) surface (ICG/Au/Pt@PDA-PEG) to attain superior cancer cell killing efficiency though win-win cooperation between starvation therapy, phototherapy, and chemodynamic therapy. The as-synthesized ICG/Au/Pt@PDA-PEG has shown excellent light-to-heat conversion (photothermal therapy) and reactive oxygen species generation (photodynamic therapy) properties upon laser irradiation and also red-shifted ICG absorption (from 780 to 800 nm) and enhanced its photostability. Further, the ICG/Au/Pt@PDA-PEG NRs have reduced the solution glucose concentration and slightly increased solution oxygen levels and also enhanced 3,3',5,5'-tetramethylbenzidine oxidation in the presence of glucose through a cascade of enzymatic activities. The in vitro results demonstrated that the ICG/Au/Pt@PDA-PEG NRs have superior therapeutic efficacy against cancer cells via the cooperative effect between starvation/photo/chemodynamic therapies and not much toxicity to normal cells.