Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO2. By adjusting the ratio of reactants, highly-ordered MnO2@PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO2 functions as catalase mimic. In this way, the well-defined MnO2@PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth.
The insufficient
intracellular H2O2 level
in tumor cells is closely associated with the limited efficacy of
chemodynamic therapy (CDT). Despite tremendous efforts, engineering
CDT agents with a straightforward and secure H2O2 supplying ability remains a great challenge. Inspired by the balance
of H2O2 generation and elimination in cancer
cells, herein, a nanozyme-based H2O2 homeostasis
disruptor is fabricated to elevate the intracellular H2O2 level through facilitating H2O2 production and restraining H2O2 elimination
for enhanced CDT. In the formulation, the disruptor with superoxide
dismutase-mimicking activity can convert O2
•– to H2O2, promoting the production of H2O2. Simultaneously, the suppression of catalase
activity and depletion of glutathione by the disruptor weaken the
transformation of H2O2 to H2O. Thus,
the well-defined system could perturb the H2O2 balance and give rise to the accumulation of H2O2 in cancer cells. The raised H2O2 level
would ultimately amplify the Fenton-like reaction-based CDT efficiency.
Our work not only paves a way to engineer alternative CDT agents with
a H2O2 supplying ability for intensive CDT but
also provides new insights into the construction of bioinspired materials.
Shutting
down glucose supply by glucose oxidase (GOx) to starve
tumors has been considered to be an attractive strategy in cancerous
starvation therapy. Nevertheless, the in vivo applications
of GOx-based starvation therapy are severely restricted by the poor
GOx delivery efficiency and the self-limiting therapeutic effect.
Herein, a biomimetic nanoreactor has been fabricated for starvation-activated
cancer therapy by encapsulating GOx and prodrug tirapazamine (TPZ)
in an erythrocyte membrane cloaked metal–organic framework
(MOF) nanoparticle (TGZ@eM). The fabricated TGZ@eM nanoreactor can
assist the delivery of GOx to tumor cells and then exhaust endogenous
glucose and O2 to starve tumors efficiently. Importantly,
the resulting tumor hypoxia by GOx-based starvation therapy further
initiates the activation of TPZ, which is released from the nanoreactor
in the acid lyso/endosome environment, for enhanced colon cancer therapy.
More importantly, by integrating the biomimetic surface modification,
the immunity-escaping and prolonged blood circulation characteristics
endow our nanoreactor dramatically improved cancer targeting ability.
The in vitro and in vivo outcomes
indicate our biomimetic nanoreactor exhibits a strong synergistic
cascade effect for colon cancer therapy in an accurate and facile
manner.
Nanozymes have emerged as a new generation of antibiotics with exciting broad‐spectrum antimicrobial properties and negligible biotoxicities. However, their antibacterial efficacies are unsatisfactory due to their inability to trap bacteria and their low catalytic activity. Herein, we report nanozymes with rough surfaces and defect‐rich active edges. The rough surface increases bacterial adhesion and the defect‐rich edges exhibit higher intrinsic peroxidase‐like activity compared to pristine nanozymes due to their lower adsorption energies of H2O2 and desorption energy of OH*, as well as the larger exothermic process for the whole reaction. This was demonstrated using drug‐resistant Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus in vitro and in vivo. This strategy can be used to engineer nanozymes with enhanced antibacterial function and will pave a new way for the development of alternative antibiotics.
Sepsis, characterized by immoderate production of multiple reactive oxygen and nitrogen species (RONS), causes high morbidity and mortality. Despite progress made with nanozymes, efficient antioxidant therapy to eliminate these RONS remains challenging, owing largely to the specificity and low activity of exploited nanozymes. Herein, an enzyme‐mimicking single‐atom catalyst, Co/PMCS, features atomically dispersed coordinatively unsaturated active Co‐porphyrin centers, which can rapidly obliterate multiple RONS to alleviate sepsis. Co/PMCS can eliminate O2.− and H2O2 by mimicking superoxide dismutase, catalase, and glutathione peroxidase, while removing .OH via the oxidative‐reduction cycle, with markedly higher activity than nanozymes. It can also scavenge .NO through formation of a nitrosyl–metal complex. Eventually, it can reduce proinflammatory cytokine levels, protect organs from damage, and confer a distinct survival advantage to the infected sepsis mice.
Silver nanoparticles (AgNPs) have been used as a broad-spectrum antimicrobial agent, whose toxicity originates from the localized release of Ag ions. However, the residual AgNPs core could generate potential risk to humans and waste of noble metals. Herein, we infused the cysteine-modified molybdenum disulfide with minimum Ag ions and coated with a layer of cationic polyelectrolyte to construct an efficient and benign antimicrobial depot. The system exhibited much enhanced broad-spectrum antibacterial activity compared with an equivalent amount of silver nitrate, owing to its increasing accessibility of released Ag to the cell walls of microorganisms. More importantly, the antibacterial system could be successfully applied to treat wound infection, while retaining high antibacterial activities, exhibiting negligible biotoxicity and avoiding the waste of Ag.
DNA metallization has witnessed tremendous growth and development, from the initial simple synthesis aimed at manufacturing conductive metal nanowires to the current fabrication of various nanostructures for applications in areas as diverse as nanolithography, energy conversion and storage, catalysis, sensing, and biomedical engineering. To this, our aim here was to present a comprehensive review to summarize the research activities on DNA metallization that have appeared since the concept was first proposed in 1998. We start with a brief presentation of the basic knowledge of DNA and its unique advantages in the template-directed growth of metal nanomaterials, followed by providing a systematic summary of the various synthetic methods developed to date to deposit metals on DNA scaffolds. Then, the leverage of DNAs with different sequences, conformations, and structures for tuning the synthesis of feature-rich metal nanostructures is discussed. Afterwards, the discussion is divided around the applications of these metal nanomaterials in the fields mentioned above, wherein the key role DNA metallization plays in enabling high performance is emphasized. Finally, the current status and some future prospects and challenges in this field are summarized. As such, this review would be of great interest to promote the further development of DNA metallization by attracting researchers from various communities, including chemistry, biology, physiology, material science, and nanotechnology as well as other disciplines.
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