Radiotherapy (RT) is a mainstay treatment for many types of cancer, although it is still a large challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are promising agents that enhance injury to tumor tissue by accelerating DNA damage and producing free radicals. Several strategies have been exploited to develop highly effective and low-toxicity radiosensitizers. In this review, we highlight recent progress on radiosensitizers, including small molecules, macromolecules, and nanomaterials. First, small molecules are reviewed based on free radicals, pseudosubstrates, and other mechanisms. Second, nanomaterials, such as nanometallic materials, especially gold-based materials that have flexible surface engineering and favorable kinetic properties, have emerged as promising radiosensitizers. Finally, emerging macromolecules have shown significant advantages in RT because these molecules can be combined with biological therapy as well as drug delivery. Further research on the mechanisms of radioresistance and multidisciplinary approaches will accelerate the development of radiosensitizers.
been widely used as promising agents for multifunctional blood vessel imaging and tumor imaging. All these agents with well-defined surface chemistry performed good stability and high fluorescence in physiological environment and can be used for NIR-II imaging in vivo. However, due to the large hydrodynamic size, most of inorganic nanoparticles still cannot be excreted rapidly by kidney. The accumulation of these materials in body may induce potential liver toxicity, which prevents their further applications in clinical medicine. Moreover, the organic materials, such as conjugated polymer fluorophores [7] and small molecules, [8] have improved biocompatibility, showing great potential in clinical translation. Nevertheless, the fluorescence quantum yield (QY) of these materials is still far from ideal. Thus, it is desirable to design an NIR-II agent with high QY as well as high efficiency in renal clearance for wide biological and clinical applications. Here, we present a bright Au 25 cluster with the unique cage-like structure that can emit NIR-II fluorescence at 1100-1350 nm by the charge transfer between ligand and gold core. [9] Metal doping further increases fluorescence QY of Au 25 clusters. The time-resolved brain blood flow shows significant differences between healthy and injured brain, which allow us to distinguish the lipopolysaccharides (LPS) induced brain injury and stroke in vivo. Meanwhile, real-time cancer metastasis is monitored by NIR-II imaging. Importantly, the ultrasmall hydrodynamic size of 3.2 nm allows the gold clusters to cross the glomerular filtration and be excreted fast by Near-infrared II (NIR-II) imaging at 1100-1700 nm shows great promise for medical diagnosis related to blood vessels because it possesses deep penetration and high resolution in biological tissue. Unfortunately, currently available NIR-II fluorophores exhibit slow excretion and low brightness, which prevents their potential medical applications. An atomic-precision gold (Au) cluster with 25 gold atoms and 18 peptide ligands is presented. The Au 25 clusters show emission at 1100-1350 nm and the fluorescence quantum yield is significantly increased by metal-atom doping. Bright gold clusters can penetrate deep tissue and can be applied in in vivo brain vessel imaging and tumor metastasis. Time-resolved brain blood-flow imaging shows significant differences between healthy and injured mice with different brain diseases in vivo. High-resolution imaging of cancer metastasis allows for the identification of the primary tumor, blood vessel, and lymphatic metastasis. In addition, gold clusters with NIR-II fluorescence are used to monitor highresolution imaging of kidney at a depth of 0.61 cm, and the quantitative measurement shows 86% of the gold clusters are cleared from body without any acute or long-term toxicity at a dose of 100 mg kg −1 .
Neurotrauma is one of the most serious traumatic injuries, which can induce an excess amount of reactive oxygen and nitrogen species (RONS) around the wound, triggering a series of biochemical responses and neuroinflammation. Traditional antioxidant-based bandages can effectively decrease infection via preventing oxidative stress, but its effectiveness is limited to a short period of time due to the rapid loss of electron-donating ability. Herein, we developed a nanozyme-based bandage using single-atom Pt/CeO2 with a persistent catalytic activity for noninvasive treatment of neurotrauma. Single-atom Pt induced the lattice expansion and preferred distribution on (111) facets of CeO2, enormously increasing the endogenous catalytic activity. Pt/CeO2 showed a 2–10 times higher scavenging activity against RONS as well as 3–10 times higher multienzyme activities compared to CeO2 clusters. The single-atom Pt/CeO2 retained the long-lasting catalytic activity for up to a month without obvious decay due to enhanced electron donation through the Mars–van Krevelen reaction. In vivo studies disclosed that the nanozyme-based bandage at the single-atom level can significantly improve the wound healing of neurotrauma and reduce neuroinflammation.
Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than natural trolox, respectively. Meanwhile, the clusterzymes demonstrate preferential enzyme-mimicking catalytic activities, with Au25, Au24Cu1 and Au24Cd1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au24Cu1 decreases peroxide in injured brain via catalytic reactions, while Au24Cd1 preferentially uses superoxide and nitrogenous signal molecules as substrates, and significantly decreases inflammation factors, indicative of an important role in mitigating neuroinflammation.
Black phosphorus (BP), as an emerging successor to layered two-dimensional materials, has attracted extensive interest in cancer therapy. Toxicological studies on BP are of great importance for potential biomedical applications, yet not systemically explored. Herein, toxicity and oxidative stress of BP quantum dots (BPQDs) at cellular, tissue, and whole-body levels are evaluated by performing the systemic in vivo and in vitro experiments. In vitro investigations show that BPQDs at high concentration (200 μg/mL) exhibit significant apoptotic effects on HeLa cells. In vivo investigations indicate that oxidative stress, including lipid peroxidation, reduction of catalase activity, DNA breaks, and bone marrow nucleated cells (BMNC) damage, can be induced by BPQDs transiently but recovered gradually to healthy levels. No apparent pathological damages are observed in all organs, especially in the spleen and kidneys, during the 30-day period. This work clearly shows that BPQDs can cause acute toxicities by oxidative stress responses, but the inflammatory reactions can be recovered gradually with time for up to 30 days. Thus, BPQDs do not give rise to long-term appreciable toxicological responses.
Metal nanozyme has attracted wide interest for biomedicine, and a highly catalytic material in the physiological environment is highly desired. However, catalytic selectivity of nanozyme is still highly challenging, limiting its wide application. Here, we show a trimetallic (triM) nanozyme with highly catalytic activity and environmental selectivity. Enzyme-mimicked investigations find that the triM system possesses multi-enzyme-mimetic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as 1O2, H2O2, •OH, and •NO. Importantly, triM nanozyme exhibits the significant neutral environment preference for removing the •OH, 1O2, and •NO free radical, indicating its highly catalytic selectivity. The density functional theory (DFT) calculations reveal that triM nanozyme can capture electrons very easily and provides more attraction to reactive oxygen and nitrogen species (RONS) radicals in the neutral environment. In vitro experiments show that triM nanozyme can improve the viability of injured neural cell. In the LPS-induced brain injury model, the superoxide dismutase (SOD) activity and lipid peroxidation can be greatly recovered after triM nanozyme treatment. Moreover, the triM nanozyme treatment can significantly improve the survival rate, neuroinflammation, and reference memory of injured mice. Present work provides a feasible route for improving selectivity of nanozyme in the physiological environment as well as exploring potential applications in brain science.
Reactive oxygen and nitrogen species (RONS), especially reactive nitrogen species (RNS) are intermediate products during incidence of nervous system diseases, showing continuous damage for traumatic brain injury (TBI). Here, we developed a carbogenic nanozyme, which shows an antioxidant activity 12 times higher than ascorbic acid (AA) and behaves as multienzyme mimetics. Importantly, the nanozyme exhibits an ultrahigh scavenging efficiency (∼16 times higher than AA) toward highly active RNS, such as •NO and ONOO– as well as traditional reactive oxygen species (ROS) including O2 •–, H2O2, and •OH. In vitro experiments show that neuron cells injured by H2O2 or lipopolysaccharide can be significantly recovered after carbogenic nanozyme treatment via scavenging all kinds of RONS. Moreover, the carbogenic nanozyme can serve as various enzyme mimetics and eliminate the harmful peroxide and glutathione disulfide from injured mice, demonstrating its potential as a therapeutic for acute TBI.
A novel nano-conjugate containing ultrasmall water-soluble AuNCs protected by ovalbumin as the fluorescent part, folic acid as the targeting ligand and a homopolymer N-acryloxysuccinimide as the linker has been investigated. Moreover, specific staining of HeLa cells by the nano-conjugate has been demonstrated.
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