The efficiency of chemical intercommunication between enzymes in natural networks can be significantly enhanced by the organized catalytic cascades. Nevertheless, the exploration of two-or-more-enzymes-engineered nanoreactors for catalytic cascades remains a great challenge in cancer therapy because of the inherent drawbacks of natural enzymes. Here, encouraged by the catalytic activity of the individual nanozyme for benefiting the treatment of solid tumors, we propose an organized in situ catalytic cascades-enhanced synergistic therapeutic strategy driven by dual-nanozymes-engineered porphyrin metal–organic frameworks (PCN). Precisely, catalase-mimicking platinum nanoparticles (Pt NPs) were sandwiched by PCN, followed by embedding glucose oxidase-mimicking ultrasmall gold nanoparticles (Au NPs) within the outer shell, and further coordination with folic acid (P@Pt@P–Au–FA). The Pt NPs effectively enabled tumor hypoxia relief by catalyzing the intratumoral H2O2 to O2 for (1) enhancing the O2-dependent photodynamic therapy and (2) subsequently accelerating the depletion of β-d-glucose by Au NPs for synergistic starving-like therapy with the self-produced H2O2 as the substrate for Pt NPs. Consequently, a remarkably strengthened antitumor efficiency with prevention of tumor recurrence and metastasis was achieved. This work highlights a rationally designed tumor microenvironment-specific nanoreactor for opening improved research in nanozymes and provides a means to design a catalytic cascade model for practical applications.

AuroShell nanoparticles (sealed gold nanoshell on silica) are the only inorganic materials that are approved for clinical trial for photothermal ablation of solid tumors. Based on that, porous gold nanoshell structures are thus critical for cancer multiple theranostics in the future owing to their inherent cargo-loading ability. Nevertheless, adjusting the diverse experimental parameters of the reported procedures to obtain porous gold nanoshell structures is challenging. Herein, a series of amino-functionalized porous metal-organic frameworks (NH -MOFs) nanoparticles are uncovered as superior templates for porous gold nanoshell deposition (NH -MOFs@Au ) by means of a more facile and general one-step method, which combines the enriched functionalities of NH -MOFs with those of porous gold nanoshells. Moreover, in order to illustrate the promising applications of this method in biomedicine, platinum nanozymes-encapsulated NH -MOFs are further designed with porous gold nanoshell coating and photosensitizer chlorin e6 (Ce6)-loaded nanoparticles with continuous O -evolving ability (Pt@UiO-66-NH @Au -Ce6). The combination of photodynamic and photothermal therapy is then carried out both in vitro and in vivo, achieving excellent synergistic therapeutic outcomes. Therefore, this work not only presents a facile strategy to fabricate functionalized porous gold nanoshell structures, but also illustrates an excellent synergistic tumor therapy strategy.

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence‐change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell‐cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi‐drug combination strategy with β‐elemene, a plant‐derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on‐demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large‐scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new‐concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

Prussian blue nanoprobes are widely studied and applied in tumor photothermal therapy (PTT) and magnetic resonance imaging (MRI), due to their low toxicity and excellent in vivo performance. However, the sizes of hitherto reported Prussian blue nanoprobes are generally larger than 50 nm, which greatly influence cell phagocytosis, in vivo circulation, and biodistribution. In this work, a novel method of doping zinc ions is used to control the size of Prussian blue nanoprobes. Consequently, the performances of the nanoprobes in PTT and MRI are both significantly improved. The results show that the minimum size of Prussian blue nanoprobes achieved by doping 10% zinc ions (abbreviated as SPBZn(10%)) is 3.8 ± 0.90 nm, and the maximum specific absorption coefficient, photothermal conversion efficiency, and longitudinal relaxation rates are 1.78 L g−1 cm−1, 47.33%, and 18.40 mm−1 s−1, respectively. In addition, the SPBZn(10%) nanoprobes provide excellent PTT efficacy on 4T1 tumor cells (killing rate: 90.3%) and breast cancer model (tumor inhibition rate: 69.4%). Toxicological experiment results show that the SPBZn(n%) nanoprobes exhibit no obvious in vitro cytotoxicity and they can be used safely in mice at doses below 100 mg kg−1. Therefore, SPBZn(10%) nanoprobes can potentially be used for effective cancer theranostics.