ABSTRACT
The uncontrolled treatment process and high concentration of intracellular glutathione compromise the therapeutic efficacies of chemodynamic therapy (CDT). Here, iron oxide nanocrystals embedded in N-doped carbon nanosheets (IONCNs) are designed as a near-infrared light-triggered nanozyme for synergistic cascade tumor therapy. The IONCNs can absorb and convert 980 nm light to local heat, which induces the dissolution of iron oxide for generating Fe2+/Fe3+ in a weak acid environment, apart from thermal ablation of cancer cells. The formed Fe2+ takes on the active site for the Fenton reaction. The formed Fe3+ acts as glutathione peroxidase to magnify oxidative stress, improving the antitumor performance. The IONCNs can be used to visually track the treatment process via magnetic resonance imaging. Such IONCNs demonstrate great potential as an exogenously triggered nanozyme via an integrated cascade reaction for imaging-guided synergistic cancer therapy.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Cell Line, Tumor , Glutathione , Humans , Hydrogen Peroxide , Magnetic Resonance Imaging , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/drug therapyABSTRACT
The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.
Subject(s)
Biomimetics , Doxorubicin/pharmacology , Manganese/pharmacology , Mitochondria/metabolism , Nanoparticles , Selenium/chemistry , Antineoplastic Agents/pharmacology , Biomass , Cell Line, Tumor , Drug Delivery Systems , Drug Therapy , HeLa Cells , Humans , Hydrogen Peroxide/metabolism , Ions , Phospholipid Hydroperoxide Glutathione Peroxidase , Reactive Oxygen Species/metabolism , Superoxide Dismutase-1ABSTRACT
Phototherapy in the second near-IR (1000-1700 nm, NIR-II) window has achieved much progress because of its high efficiency and relatively minor side effects. In this paper, a new NIR-II responsive hollow magnetite nanocluster (HMNC) for targeted and imaging-guided cancer therapy is reported. The HMNC not only provides a hollow cavity for drug loading but also serves as a contrast agent for tumor-targeted magnetic resonance imaging. The acid-induced dissolution of the HMNCs can trigger a pH-responsive drug release for chemotherapy and catalyze the hydroxyl radical (·OH) formation from the decomposition of hydrogen peroxide for chemodynamic therapy. Moreover, the HMNCs can adsorb and convert NIR-II light into local heat (photothermal conversion efficacy: 36.3%), which can accelerate drug release and enhance the synergistic effect of chemo-photothermal therapy. The HMNCs show great potential as a versatile nanoplatform for targeted imaging-guided trimodal cancer therapy.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Doxorubicin , Drug Liberation , Ferrosoferric Oxide , Magnetic Resonance Imaging , PhototherapyABSTRACT
Both green tea (GT) extract and vitamin C (VC) were used for the reduction of Fe3+ to Fe0 using a green synthesis method. Modified nanozero-valent iron (GT-nZVI@VC nanocomposites) was successfully obtained and characterized as α-Fe0-iron oxide/VC by multiple analytical methods. The GT-nZVI@VC nanocomposites showed better transportability than nZVI, in that transport behavior was slightly dependent on various ratios of sand/soil in water-saturated heterogeneous porous media. Breakthrough curves of GT-nZVI@VC nanocomposites in paddy soil exhibited "blocking effects" and were well described using a first-order straining coefficient (k2) on site 2 obtained from a two-site kinetic attachment model. In particular, GT-nZVI@VC (VC/Fe = 0.6) showed higher Cr(VI) removal (especially reducibility) in both paddy soil and water compared to that of nZVI and VC. It is likely that the synergistic effects of VC (ascorbic acid) and tea polyphenols can increase the released free electrons into solution, favoring the high reduction of Cr(VI) into Cr(III) (i.e., FeOCr2O3, Cr(OH)3 and Cr2O3), where Cr(III) is prone to be immobilized by the nanocomposites in soil. This research highlights that VC can mediate the activation of GT extract to successfully modify nZVI, which could be beneficial for efficient transport in subsurface and remediation of Cr(VI)-contaminated soil and underground water.
Subject(s)
Iron , Water Pollutants, Chemical , Ascorbic Acid , Chromium/analysis , Plant Extracts , Porosity , Tea , Water Pollutants, Chemical/analysisABSTRACT
Rational design of metal-free multifunctional therapeutic reagents offers great opportunities for cancer treatment in the clinic. Here, graphitic carbon nitride (g-C3N4) quantum dots embedded in carbon nanosheets (CNQD-CN) are in situ prepared via a one-pot hydrothermal approach with formamide as carbon and nitrogen source. The CNQD-CN not only serves as an excellent near-infrared (NIR) fluorescent marker but also acts as a pH-responsive nanocarrier. Moreover, the CNQD-CN possesses both light-to-heat conversion and singlet oxygen generation capabilities under a single NIR excitation wavelength. Further investigations show that systemic delivery of doxorubicin (DOX) using the multifunctional CNQD-CN nanocarrier under NIR irradiation was highly effective to cause cancer cell apoptosis in vitro and inhibit tumor growth in vivo. CNQD-CN represents a multifunctional therapeutic platform for synchronous cancer imaging and treatment through the synergistic effect of phototherapy and chemotherapy.
Subject(s)
Graphite , Quantum Dots , Carbon , Doxorubicin/pharmacology , Nitrogen CompoundsABSTRACT
Oxidative stress plays a crucial role in ammonia nitrogen toxicity. In this study, the beneficial effects of dietary nano cerium oxide (nano CeO2) as a potent antioxidant were examined in the Chinese mitten crab (Eriocheir sinensis). Crabs were fed a diet supplemented with 0, 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, or 12.8â¯mg/kg nano CeO2 for 60â¯d. The optimum supplementation level of nano CeO2 that significantly increased weight gain rate and decreased feed coefficient was 0.8â¯mg/kg. This level also offered immune protection when crabs were kept under ammonia nitrogen stress and/or exposed to pathogen infection (Aeromonas hydrophila). Supplementation with 0.8â¯mg/kg of CeO2 (i) relieved pathological damage to the hepatopancreas; (ii) increased hemocyte counts, including total number of hemocytes, granulocytes, and hyalinocytes; (iii) decreased malondialdehyde content and increased antioxidant enzyme activities of superoxide dismutase and catalase in the hemolymph; (iv) increased the activities of lysozyme, acid phosphatase, and alkaline phosphatase in the hemolymph; and (v) increased gene and protein expression of cathepsin L in the hepatopancreas. Mortality increased when crabs were injected with bacteria under ammonia nitrogen stress, but dietary supplementation with 0.8â¯mg/kg nano CeO2 decreased the mortality rate. Thus, the results of this study suggested that dietary supplementation with nano CeO2 in crabs promoted growth and up-regulated immunity to bacterial infection under ammonia nitrogen stress.