Nanozyme-Based Regulation of Cellular Metabolism and Their Applications.

Metabolism is the sum of the enzyme-dependent chemical reactions, which produces energy in catabolic process and synthesizes biomass in anabolic process, exhibiting high similarity in mammalian cell, microbial cell, and plant cell. Consequently, the loss or gain of metabolic enzyme activity greatly affects cellular metabolism. Nanozymes, as emerging enzyme mimics with diverse functions and adjustable catalytic activities, have shown attractive potential for metabolic regulation. Although the basic metabolic tasks are highly similar for the cells from different species, the concrete metabolic pathway varies with the intracellular structure of different species. Here, the basic metabolism in living organisms is described and the similarities and differences in the metabolic pathways among mammalian, microbial, and plant cells and the regulation mechanism are discussed. The recent progress on regulation of cellular metabolism mainly including nutrient uptake and utilization, energy production, and the accompanied redox reactions by different kinds of oxidoreductases and their applications in the field of disease therapy, antimicrobial therapy, and sustainable agriculture is systematically reviewed. Furthermore, the prospects and challenges of nanozymes in regulating cell metabolism are also discussed, which broaden their application scenarios.

Glutathione-Induced In Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy.

Most tumor treatments will fail when ignoring competition and cooperation between each cancer cell and its microenvironment. Inspired by game theory, therapeutic agents can be introduced to compete for intracellular molecules to disrupt the cooperation between molecules and cells. Biomineralized oxidized (-)-epigallocatechin-3-o-gallate (EGCG)-molybdenum ion coordination nanoparticles were prepared for disrupting redox equilibria and simultaneously reacting with intracellular GSH in a Michael addition to form large aggregates that can mechanically disrupt endosomal and plasma membranes, stimulating pyroptosis and anti-tumor immunological responses for versatile inhibition of different types of tumors. This design disrupts the cooperation between molecules and between cancer and immune cells, achieving an optimal payoff in competition and cooperation in cancer therapy.

Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy.

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.

Precise Subcellular Organelle Targeting for Boosting Endogenous-Stimuli-Mediated Tumor Therapy.

Though numerous external-stimuli-triggered tumor therapies, including phototherapy, radiotherapy, and sonodynamic therapy have made great progress in cancer therapy, the low penetration depth of the laser, safety concerns of radiation, the therapeutic resistance, and the spatio-temporal constraints of the specific equipment restrict their convenient clinical applications. What is more, the inherent physiological barriers of the tumor microenvironment (TME), including hypoxia, heterogeneity, and high expression of antioxidant molecules also restrict the efficiency of tumor therapy. As a result, the development of nanoplatforms responsive to endogenous stimuli (such as glucose, acidic pH, cellular redox events, and etc.) has attracted great attention for starvation therapy, ion therapy, prodrug-mediated chemotherapy, or enzyme-catalyzed therapy. In addition, nanomedicines can be modified by some targeted units for precisely locating in subcellular organelles and boosting the destroying of tumor tissue, decreasing the dosage of nanoagents, reducing side effects, and enhancing the therapeutic efficiency. Herein, the properties of the TME, the advantages of endogenous stimuli, and the principles of subcellular-organelle-targeted strategies will be emphasized. Some necessary considerations for the exploitation of precision medicine and clinical translation of multifunctional nanomedicines in the future are also pointed out.

Nanomaterials for the regulation of the tumor microenvironment and theranostics.

Cancer has become one of the primary threats to human beings, and traditional therapies (including surgery, chemotherapy and radiotherapy) show limited therapeutic efficacy due to the complexity of tumor biology. Furthermore, determining how to utilize the differences between the tumor microenvironment (TME) and healthy tissues and exploring new nanoplatforms that can realize early diagnosis and effective and non-toxic therapy are challenges in cancer theranostics. Numerous researchers have designed multifunctional nanomaterials and investigated their personalized therapy and regulation abilities toward TME, including oxygen generation, glutathione consumption and the production of reactive oxygen species and multi-model imaging effects. This review will introduce the latest progress in the design of multi-functional nanomedicines for the regulation of TME and their theranostics, and it will provide a critical angle for the future development of nanomedicine.

Biodegradable iron-coordinated hollow polydopamine nanospheres for dihydroartemisinin delivery and selectively enhanced therapy in tumor cells.

As the semisynthetic derivative and active metabolite of the effective anti-malarial drug artemisinin, dihydroartemisinin (DHA) has been investigated as an emerging therapeutic agent for tumor treatment based on the cytotoxicity of free-radicals originating from interactions with ferrous ions. Meanwhile, simultaneously delivering DHA and iron ions to tumors for selectively killing cancer cells is still a great challenge in DHA tumor therapy. Herein, we develop a facile yet efficient strategy based on iron-coordinated hollow polydopamine nanospheres to load DHA (DHA@HPDA-Fe). The as-prepared nanoagent is biodegradable and exhibits controllable release of DHA and Fe ions in tumor microenvironments, resulting in ferrous ion-enhanced production of cytotoxic reactive oxygen species (ROS) by DHA and thus effectively killing the tumor cells. In vivo therapy experiments indicated that the anti-tumor efficacy of DHA@HPDA-Fe was about 3.05 times greater than that of free DHA, and the tumor inhibition ratio was 88.7% compared with the control group, accompanied by negligible side effects, indicating that the proposed nanomedicine platform is promising for anti-tumor applications.

Gram-scale fabrication of Bi@C nanoparticles through one-step hydrothermal method for dual-model imaging-guided NIR-II photothermal therapy.

At present, increasing attention is being paid to photothermal therapy corresponding to the second near infrared (NIR-II) range (1000-1700 nanometers); however, its biomedical applications related to carbon-based nanomaterials (CNMs) have always been limited by the large-scale fabrication of excellent diagnostic probes with a suitable size and optical absorption cross-section. Herein, we successfully prepared Bi@C nanoparticles with a suitable size and high output (3.14 g per patch) through a one-pot hydrothermal method. By combining Bi with carbon, the optical absorption in the NIR-II range was enhanced compared to that for single carbon; moreover, Bi@C could no longer be easily oxidized due to the protection of outer C compared with individual Bi. Furthermore, because of the high atomic number of Bi (Z = 83), the Bi@C nanoparticles exhibited computed imaging contrast properties. According to the in vitro and in vivo experiments, the Bi@C nanoparticles could ablate cancer cells under illumination with a 1064 nm laser with deeper penetration and an appropriate permissible exposure (MPE) to the laser (1 W cm-2), showing excellent performance for the diagnosis and treatment of tumors. This study provides a simple method to synthesize metal-carbon nanocomposites to enhance the NIR-II optical absorption efficiency for effective deep-seated tumor photothermal therapy and will further broaden the applications of CNMs.

Ce(III, IV)-MOF electrocatalyst as signal-amplifying tag for sensitive electrochemical aptasensing.

Metal-organic frameworks (MOFs) as a new class of porous materials have attracted increasing attention in the field of biomimetic catalysis. This study firstly reports a mixed valence state Ce-MOF possessing intrinsic catalytic activity towards thionine (Thi), and its application in constructing an amplified electrochemical aptasensor for thrombin detection. As noticed, the novel catalytic process combines the advantages of 3D infinite extension of the Ce(III, IV)-MOF skeleton containing large amounts of catalytic sites and spontaneous recycling of the Ce(III)/Ce(IV) for electrochemical reduction of Thi, thereby presenting amplified electrochemical signals. To further improve the aptasensor performance, the high selectivity of proximity binding-induced DNA strand displacement and high efficiency of exonuclease III-assisted recycling amplification were incorporated into the assay. The aptasensor was employed to detect thrombin in complex serum samples, which shows high sensitivity, specificity, stability and reproducibility. This work offers an opportunity to develop MOF-based electrocatalyst as signal-amplifying tag for versatile bioassays and catalytic applications.