Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8 + cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8 + cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIO-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.

In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both in vitro and in vivo results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive in vivo systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6–18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.

Metastasis remains the major cause of death in cancer patients. Thus, there is a need to sensitively detect tumor metastasis, especially ultrasmall metastasis, for early diagnosis and precise treatment of cancer. Herein, an ultrasensitive T1‐weighted magnetic resonance imaging (MRI) contrast agent, UMFNP‐CREKA is reported. By conjugating the ultrasmall manganese ferrite nanoparticles (UMFNPs) with a tumor‐targeting penta‐peptide CREKA (Cys‐Arg‐Glu‐Lys‐Ala), ultrasmall breast cancer metastases are accurately detected. With a behavior similar to neutrophils' immunosurveillance process for eliminating foreign pathogens, UMFNP‐CREKA exhibits a chemotactic “targeting‐activation” capacity. UMFNP‐CREKA is recruited to the margin of tumor metastases by the binding of CREKA with fibrin‐fibronectin complexes, which are abundant around tumors, and then release of manganese ions (Mn2+) to the metastasis in response to pathological parameters (mild acidity and elevated H2O2). The localized release of Mn2+ and its interaction with proteins affects a marked amplification of T1‐weighted magnetic resonance (MR) signals. In vivo T1‐weighted MRI experiments reveal that UMFNP‐CREKA can detect metastases at an unprecedented minimum detection limit of 0.39 mm, which has significantly extended the detection limit of previously reported MRI probe.

Controlling the size, shape and structure of nanocrystals is technologically important because of the strong effect of size and shape on optical, electrical, and catalytic properties. Monodispersed nanocrystals of copper oxide were prepared by the precipitation–pyrolysis method. By controlling the starting materials, reactive concentration and annealing temperature, we can obtain spherical monodispersed CuO nanocrystals of different sizes or rodlike CuO nanocrystals. The particle sizes of CuO monodispersed nanocrystals can be tuned in the range between and 30 nm. The products have been characterized by x-ray diffraction, transmission electron microscopy, high-resolution transmission electron microscopy and the UV–visible absorption spectrum. The absorption spectra of CuO nanocrystals show clear evidence of the quantum size effect. The possible formation mechanism of monodispersed CuO nanocrystals is discussed.

The recent emergence of numerous nanotechnologies is expected to facilitate the development of regenerative medicine, which is a tissue regeneration technique based on the replacement/repair of diseased tissue or organs to restore the function of lost, damaged, and aging cells in the human body. In particular, the unique magnetic properties and specific dimensions of magnetic nanomaterials make them promising innovative components capable of significantly advancing the field of tissue regeneration. Their potential applications in tissue regeneration are the focus here, beginning with the fundamentals of magnetic nanomaterials. How nanomaterials—both those that are intrinsically magnetic and those that respond to an externally applied magnetic field—can enhance the efficiency of tissue regeneration is also described. Applications including magnetically controlled cargo delivery and release, real‐time visualization and tracking of transplanted cells, magnetic regulation of cell proliferation/differentiation, and magnetic activation of targeted ion channels and signal pathways involved in regeneration are highlighted, and comments on the perspectives and challenges in magnetic nanomaterial‐based tissue regeneration are given.

The development of a highly efficient, low-toxicity, ultrasmall ferrite nanoparticle-based T 1 contrast agent for high-resolution magnetic resonance imaging (MRI) is highly desirable. However, the correlations between the chemical compositions, in vitro T 1 relaxivities, in vivo nano-bio interactions and toxicities remain unclear, which has been a challenge in optimizing the in vivo T 1 contrast efficacy. Methods : Ultrasmall (3 nm) manganese ferrite nanoparticles (Mn x Fe 3-x O 4 ) with different doping concentrations of the manganese ions (x = 0.32, 0.37, 0.75, 1, 1.23 and 1.57) were used as a model system to investigate the composition-dependence of the in vivo T 1 contrast efficacy. The efficacy of liver-specific contrast-enhanced MRI was assessed through systematic multiple factor analysis, which included the in vitro T 1 relaxivity, in vivo MRI contrast enhancement, pharmacokinetic profiles (blood half-life time, biodistribution) and biosafety evaluations ( in vitro cytotoxicity testing, in vivo blood routine examination, in vivo blood biochemistry testing and H&E staining to examine the liver). Results : With increasing Mn doping, the T 1 relaxivities initially increased to their highest value of 10.35 mM -1 s -1 , which was obtained for Mn 0.75 Fe 2.25 O 4 , and then the values decreased to 7.64 m M -1 s -1 , which was obtained for the Mn 1.57 Fe 1.43 O 4 nanoparticles. Nearly linear increases in the in vivo MRI signals (ΔSNR) and biodistributions (accumulation in the liver) of the Mn x Fe 3-x O 4 nanoparticles were observed for increasing levels of Mn doping. However, both the in vitro and in vivo biosafety evaluations suggested that Mn x Fe 3-x O 4 nanoparticles with high Mn-doping levels (x > 1) can induce significant toxicity. Conclusion : The systematic multiple factor assessment indicated that the Mn x Fe 3-x O 4 (x = 0.75-1) nanoparticles were the optimal T 1 contrast agents with higher in vivo efficacies for liver-specific MRI than those of the other compositions of the Mn ...

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Reactive oxygen species (ROS), a group of oxygen derived radicals and derivatives, can induce cancer cell death via elevated oxidative stress. A spatiotemporal approach with safe and deep‐tissue penetration capabilities to elevate the intracellular ROS level is highly desirable for precise cancer treatment. Here, a mechanical‐thermal induction therapy (MTIT) strategy is developed for a programmable increase of ROS levels in cancer cells via assembly of magnetic nanocubes integrated with alternating magnetic fields. The magneto‐based mechanical and thermal stimuli can disrupt the lysosomes, which sequentially induce the dysfunction of mitochondria. Importantly, intracellular ROS concentrations are responsive to the magneto‐triggers and play a key role for synergistic cancer treatment. In vivo experiments reveal the effectiveness of MTIT for efficient eradication of glioma and breast cancer. By remote control of the force and heat using magnetic nanocubes, MTIT is a promising physical approach to trigger the biochemical responses for precise cancer treatment.