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Abstract The secondary injury is more serious after traumatic brain injury (TBI) compared with primary injury. Release of excessive reactive oxygen species (ROS) and Ca2+ influx at the damaged site trigger the secondary injury. Herein, a neutrophil-like cell membrane-functionalized nanoparticle was developed to prevent ROS-associated secondary injury. NCM@MP was composed of three parts: (1) Differentiated neutrophil-like cell membrane (NCM) was synthesized, with inflammation-responsive ability to achieve effective targeting and to increase the retention time of Mn3O4 and nimodipine (MP) in deep injury brain tissue via C-X-C chemokine receptor type 4, integrin beta 1 and macrophage antigen-1. (2) Nimodipine was used to inhibit Ca2+ influx, eliminating the ROS at source. (3) Mn3O4 further eradicated the existing ROS. In addition, NCM@MP also exhibited desirable properties for T1 enhanced imaging and low toxicity which may serve as promising multifunctional nanoplatforms for precise therapies. In our study, NCM@MP obviously alleviated oxidative stress response, reduced neuroinflammation, protected blood–brain barrier integrity, relieved brain edema, promoted the regeneration of neurons, and improved the cognition of TBI mice. This study provides a promising TBI management to relieve the secondary spread of damage. Graphical Abstract

Abstract Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy. Graphical Abstract

Acute kidney injury (AKI) induced by cisplatin (DDP), which is accompanied with the generation of reactive oxygen species (ROS), is a severe side effect during treatment and restricts the application of DDP. In this study, we develop ultrasmall Mn3O4 nanozyme (UMON) with tumor microenvironment (TME) responsive ROS scavenging and generating as adjuvant to alleviate DDP induced AKI with improved efficacy. In kidney, UMON with superoxide dismutase and catalase activity acts as ROS scavenger to eliminate ROS generated by DDP, successfully protecting the renal cells/tissue and alleviating AKI during DDP treatment. Alternatively, UMON rapidly responses to the high GSH level in TME and release Mn2+ in tumor. This unique feature endows it to generate hydroxyl radicals (∙OH) through a Fenton-like reaction and deplete GSH in tumor cell and tissue, achieving high efficient chemodynamic therapy (CDT). More importantly, the Mn2+ successfully activates the cGAS-STING pathway, initiating the immune response and effectively inhibiting the tumor metastases. The synergistic CDT and immune therapy effectively improve the anti-tumor efficacy of DDP in vitro and in vivo. This study demonstrates that TME responsive ROS scavenger/generator shows the potential to reduce side effects of DDP while improve its therapeutic efficacy, providing a new avenue to achieve efficient chemotherapy and promoting the progress of clinical chemotherapy.

Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review which comprehensively summarizes the recent development of IONP as traditional T2 CA and its new application for different modality of MRI, such as T1 imaging, simultaneous T2/T1 or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T2 and T1 modal based on quantum mechanical outer sphere and Solomon–Bloembergen–Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r2 or r1 values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.

Since manganese oxide nanomaterials attract wide attention in the biomedical and energy fields, understanding the inner relationship between their properties and structures is fundamental and urgently needed. However, controllable synthesis of metal oxide nanomaterials with diverse morphologies is still a persistent challenge. Herein, various anisotropic manganese oxide nanostructures from zero-dimensional (0-D) to three-dimensional (3-D) were successfully fabricated through thermal decomposition. We observed that chloride ions can assist the formation of 0-D nanooctaherals, nanocubes, and nanooctapods due to its binding capacity to the manganese ions on the nanocrystal surface. Interestingly, the procedural heating process can affect the decomposition rate of the manganese–oleate, which drives a substantial reduction in the surface free energy by sharing a common crystallographic orientation and leads to the formation of 1-D and 3-D nanostructures by oriented attachment growth. On the basis of systematic analyses, surface-to-volume ratio, surface manganese ion density, and geometrical confinement determined by specific morphology are found to be the key parameters to achieve high-performance T1 relaxivity. Moreover, the screened out manganese oxide nanocubes with high r1 value exhibit good contrast ability in T1-weighted MRI imaging in vitro and in vivo, showing a great potential for lesion detection in T1 contrast imaging. This study builds a link between controllable synthesis of manganese oxide nanomaterials and its property and, thus, provides a rational design clue to develop high-performance magnetic oxide nanomaterials, especially in the biomedical and energy fields. [ABSTRACT FROM AUTHOR]

Cation exchange is a powerful means to adjust the properties of nanocrystals through composition change with morphology retention. Herein, we demonstrate that cation exchange can engineer the composition of iron oxide nanocrystals to dramatically improve their contrast ability in magnetic resonance imaging (MRI). We successfully construct manganese and zinc engineered iron oxide nanoparticles with diverse shapes (sphere, cube, and octapod) by facile cation exchange reactions. Extended X-ray absorption fine structure (EXAFS) study indicates that Mn2+ and Zn2+ ions are doped into the crystal lattice of ferrite, and more importantly, most of them are distributed in Td sites of ferrite. These engineered shaped-anisotropic iron oxide nanoparticles exhibit both high saturated magnetization and large effective boundary radii, which leads to remarkable transverse relaxivity (r2), for example, 754.2 mM-1 s-1 for zinc engineered octapod iron oxide nanoparticles. These engineered iron oxide nanoparticles, as high-performance T2 contrast agents for in vivo MR imaging, enable sensitive imaging of early hepatic tumors and metastatic hepatic tumors (as small as 0.4 mm), holding great promise for prompt and accurate diagnosis of cancers and metastases. [ABSTRACT FROM AUTHOR]

We combined silver and iron oxide nanoparticles to make unique Ag@Fe2O3yolk–shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe2O3–Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe2O3yolk–shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment. [ABSTRACT FROM AUTHOR]

Postoperative recurrence and metastasis are the major problems for the current treatment of hepatocellular carcinomas (HCC) in the clinic, including hepatectomy and liver transplantation. Here, we report that arsentic-loaded nanoparticles (ALNPs) are able to reduce the invasion of HCC cells in vitro, and, more importantly, can strongly suppress the invasion and metastasis of HCC in vivo without adverse side effects. Compared to free drug arsenic trioxide , ALNPs can deliver the drug into cancer cells more efficiently, destroy the structure of microtubules and reduce the aggregation of microfilaments in cell membranes more significantly. Furthermore, our results also reveal that tumor cells in murine blood were reduced remarkably after intravenous injection of ALNPs, indicating that this nano-drug may efficiently kill circulating tumor cells in vivo. In conclusion, our nano-drug ALNPs have great potential for the suppression of metastasis of HCC, which may open up a new avenue for the effective treatment of HCC without metastasis and recurrence. [ABSTRACT FROM AUTHOR]