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.

Strategic Assessment of Boron-Enriched Carbon Dots/Naproxen: Diagnostic, Toxicity, and In Vivo Therapeutic Evaluation.

Cancer is a significant global public health concern, ranking as the leading cause of mortality worldwide. This study thoroughly explores boron-doped carbon dots (B-CDs) through a simple/rapid microwave-assisted approach and their versatile applications in cancer therapy. The result was highly uniform particles with an average diameter of approximately 4 nm. B-CDs exhibited notable properties, including strong fluorescence with a quantum yield of 33%. Colloid stability tests revealed their robustness within a pH range of 6-12, NaCl concentrations up to 0.5 M, and temperatures ranging from 30 to 60 °C. The study also delved into the kinetics of naproxen release from B-CDs as a drug delivery system. The loading efficacy of naproxen exceeded 55.56%. Under varying pH conditions, the release of naproxen from B-CDs conformed to the Peppas-Sahlin model, demonstrating the potential of Naproxen-loaded CDs for cancer drug delivery. In vitro cytotoxicity assessments, conducted using the CCK-8 Assay and flow cytometry, consistently indicated low toxicity with average cell viability exceeding 80%. An in vivo toxicity test on female mice administered 20 mg/kg of B-CDs for 31 days revealed reversible histological changes in the liver and kidneys, while the pancreas remained unaffected. Importantly, B-CDs did not impact the mice's physical behavior, body weight, or survival. In vivo experiments targeting benzo(a)pyrene-induced fibrosarcoma demonstrated the efficacy of B-CDs as naproxen carriers in the treatment of cancer. This in vivo study provides a thorough comprehension of B-CDs synthesis and toxicity and their potential applications in cancer therapy and drug delivery systems.

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.

Naproxen release from carbon dot coated magnetite nanohybrid as versatile theranostics for HeLa cancer cells.

Nanohybrid magnetite carbon dots (Fe3O4@CDs) were successfully synthesized to improve their applicability in multi-response bioimaging. The nanohybrid was prepared via pyrolysis and further loaded with naproxen (NAP) to promote drug delivery features. The characterization of the synthesized Fe3O4@CDs demonstrated the existence of Fe3O4 crystals by matching with JCPDS 75-0033 and its narrow size distribution at 11.30 nm; further, FTIR spectra confirmed the presence of Fe-O groups, C-O stretching, C-H sp2, and C-O bending, along with dual-active fluorescence and magnetic responses. The nanohybrids also exhibit particular properties such as a maximum wavelength of 230.5 nm, maximum emission in the 320-420 nm range, and slight superparamagnetic reduction (Fe3O4: 0.93620 emu per g; Fe3O4@CDs: 0.64784 emu per g). The cytotoxicity assessment of the nanohybrid revealed an excellent half-maximal inhibitory concentration (IC50) of 17 671.5 ± 1742.6 µg mL-1. Then, the incorporation of NAP decreased the cell viability to below 10%. The kinetic release properties of NAP are also confirmed as pH-dependent, and they follow the Korsmeyer-Peppas kinetics model. These results indicated that the proposed Fe3O4@CDs can be used as a new model for theranostic treatment.

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.

Comparison Direct Synthesis of Hyaluronic Acid-Based Carbon Nanodots as Dual Active Targeting and Imaging of HeLa Cancer Cells.

The present study explores the potential of carbon nanodots (CDs) synthesized from hyaluronic acid using microwave-assisted and furnace-assisted methods as bioimaging agents for cancer cells. The investigation on the effect of microwave-assisted and furnace-assisted times (2 min and 2 h) on determining CD character is dominantly discussed. Various CDs, such as HA-P1 and HA-P2 were, respectively, synthesized through the furnace-assisted method at 270 °C for 2 min and 2 h, whereas HA-M1 and HA-M2 were synthesized with the microwave-assisted method for 2 min and 2 h, respectively. Overall, various CDs were produced with an average diameter, with the maximum absorption of HA-P1, HA-P2, HA-M1, and HA-M2 at 234, 238, 221, and 217 nm, respectively. The photoluminescence spectra of these CDs showed particular emissions at 320 nm and excitation wavelengths from 340 to 400 nm. Several characterizations such as X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy reveal the CD properties such as amorphous structures, existence of D bands and G bands, and hydrophilic property supported with hydroxyl and carboxyl groups. The quantum yields of HA-M1, HA-M2, HA-P1, and HA-P2 were 12, 7, 9, and 23%, respectively. The cytotoxicity and in vitro activity were verified by a cell counting kit-8 assay and confocal laser scanning microscopy, which show a low toxicity with the percentage of living cells above 80%.

Naproxen release aspect from boron-doped carbon nanodots as a bifunctional agent in cancer therapy.

In this present study, boron-carbon nanodots were synthesized by the hydrothermal method. Boron-carbon nanodots were prepared by varying the concentration ratios of boronic acid and citric acid: 1 : 25, 2 : 1, and 25 : 1, respectively. The precursors were then poured into a Teflon autoclave and heated at 240° for 4 h. This research aims to synthesise and evaluate the potential of boron-carbon nanodots as a bioimaging agent and naproxen delivery carrier. An X-ray diffractogram showed that the boron-carbon nanodots were amorphous. To analyse the functional groups, FTIR and XPS analysis was carried out. Spectrofluorometric analysis (λ ex 320 nm) showed that the formulation of boron-carbon nanodots 2 : 1 (BCD 2 : 1) has the most ideal fluorescent properties at λ em 453 nm, whereas UV-vis analysis showed λ max at 223 nm, with a quantum yield of 52.29%. A confocal laser scanning micrograph and toxicity test (MTT assays) showed that boron-carbon nanodots delivered naproxen efficiently with loading amount and loading efficiency of naproxen 28% and 65%, respectively. Furthermore, it induced an anticancer effect in HeLa cells. This result indicated that boron-carbon nanodots can be used as a bioimaging agent and naproxen delivery carrier.

Comparison of the effects of synthesis methods of B, N, S, and P-doped carbon dots with high photoluminescence properties on HeLa tumor cells.

Although heteroatom doping is widely used to promote the optical properties of carbon dots for biological applications, the synthesis process still has problems such as multi-step process, complicating the setting of instrument along with uncontrolled products. In the present study, some elements such as boron, nitrogen, sulfur, and phosphor were intentionally doped into citric acid-based carbon dots by furnace- and microwave-assisted direct and simple carbonization processes. The process produced nanoparticles with an average diameter of 5-9 nm with heteroatoms (B, N, S, and P) placed on the core and surface of carbon dots. Among the doped carbon dots prepared, boron-doped carbon dots obtained by the microwave-assisted (B-CDs2) process showed the highest photoluminescence intensity with a quantum yield (QY) of about 32.96%. All obtained carbon dots exhibit good stability (at pH 6-12 and high ionic strength concentrations up to 0.5 M), whereas cytotoxicity analysis showed that all doped carbon dots are low-toxic with an average cell viability percentage above 80% up to 500 µg mL-1. It can be observed from the CLSM image of all doped carbon dots that the doping process not only increases the QY percentage, but also might accelerate the HeLa uptake on it and produce strong carbon dot emission at the cytoplasm of the cell. Thus, the proposed synthesis process is promising for high-potency bioimaging of HeLa cancer cells.