Magnetic nanoparticles (MNPs) functionalized with targeting moieties can recognize specific cell components and induce mechanical actuation under magnetic field. Their size is adequate for reaching tumors and targeting cancer cells. However, due to the nanometric size, the force generated by MNPs is smaller than the force required for largely disrupting key components of cells. Here, we show the magnetic assembly process of the nanoparticles inside the cells, to form elongated aggregates with the size required to produce elevated mechanical forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high magnetization, and functionalized with the epidermal growth factor (EGF) peptide for targeting cancer cells. Under a low frequency rotating magnetic field at 15 Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated hundreds of pN to dramatically damage the plasma and lysosomal membranes. The physical disruption, including leakage of lysosomal hydrolases into the cytosol, led to programmed cell death and necrosis. Our work provides a novel strategy of designing magnetic nanomedicines for mechanical destruction of cancer cells.

Background: Pathological cardiac fibrosis and hypertrophy, the common features of left ventricular remodeling, often progress to heart failure. Forkhead box transcription factor P1 (Foxp1) in endothelial cells (ECs) has been shown to play an important role in heart development. However, the effect of EC-Foxp1 on pathological cardiac remodeling has not been well clarified. This study aims to determine the role of EC-Foxp1 in pathological cardiac remodeling and the underlying mechanisms. Methods: Foxp1 EC-specific loss-of-function and gain-of-function mice were generated, and an angiotensin II infusion or a transverse aortic constriction operation mouse model was used to study the cardiac remodeling mechanisms. Foxp1 downstream target gene transforming growth factor-β1 (TGF-β1) was confirmed by chromatin immunoprecipitation and luciferase assays. Finally, the effects of TGF-β1 blockade on EC-Foxp1 deletion–mediated profibrotic and prohypertrophic phenotypic changes were further confirmed by pharmacological inhibition, more specifically by RGD-peptide magnetic nanoparticle target delivery of TGF-β1–siRNA to ECs. Results: Foxp1 expression is significantly downregulated in cardiac ECs during angiotensin II–induced cardiac remodeling. EC-Foxp1 deletion results in severe cardiac remodeling, including more cardiac fibrosis with myofibroblast formation and extracellular matrix protein production, as well as decompensated cardiac hypertrophy and further exacerbation of cardiac dysfunction on angiotensin II infusion or transverse aortic constriction operation. In contrast, EC-Foxp1 gain of function protects against pathological cardiac remodeling and improves cardiac dysfunction. TGF-β1 signals are identified as Foxp1 direct target genes, and EC-Foxp1 deletion upregulates TGF-β1 signals to promote myofibroblast formation through fibroblast proliferation and transformation, resulting in severe cardiac fibrosis. Moreover, EC-Foxp1 deletion enhances TGF-β1–promoted endothelin-1 expression, which significantly increases cardiomyocyte size and reactivates cardiac fetal genes, leading to pathological cardiac hypertrophy. Correspondingly, these EC-Foxp1 deletion–mediated profibrotic and prohypertrophic phenotypic changes and cardiac dysfunction are normalized by the blockade of TGF-β1 signals through pharmacological inhibition and RGD-peptide magnetic nanoparticle target delivery of TGF-β1–siRNA to ECs. Conclusions: EC-Foxp1 regulates the TGF-β1–endothelin-1 pathway to control pathological cardiac fibrosis and hypertrophy, resulting in cardiac dysfunction. Therefore, targeting the EC–Foxp1–TGF-β1–endothelin-1 pathway might provide a future novel therapy for heart failure.

In this study, a biocompatible nanoplatform has been constructed on the basis of magnetic mesoporous silica nanoparticles (Fe3O4@mSiO2) via surface modification of triphenylphospine (TPP) and then conjugation with fluorescent carbon dots (CDs). The as-prepared Fe3O4@mSiO2-TPP/CDs nanoplatform shows a very low cytotoxicity and apoptosis rate in various cell lines such as A549, CHO, HeLa, SH-SY5Y, HFF, and HMEC-1. More importantly, this nanoplatform integrates long time cell imaging, mitochondria-targeting, and magnetic field-enhanced cellular uptake functionalities into an all-in-one system. Time-dependent mitochondrial colocalization in all of the cell lines has been proved by using confocal laser scanning microscopy and flow cytometry, while the multicolored fluorescence of the Fe3O4@mSiO2-TPP/CDs could remain bright and stable after coincubation for 24 h. In addition, the cellular uptake efficiency could be enhanced in a short time as a static magnetic field of 0.30 T was applied to the coincubation system of A549 and HFF cell lines. This bionanoplatform may have potential applications in targeted drug delivery for mitochondria diseases as well as early cancer diagnosis and treatment.

Monodispersed ferroelectric BaTiO3 nanoparticles are synthesized as a model system to investigate the effect of ferroelectricity on a photocatalytic process. The results demonstrate that ferroelectricity can directly affect the photocatalytic activity due to promotion of the separation of photo-excited carriers by spontaneous polarization in ferroelectric materials. Moreover, Ag nanoparticles are attached on these BaTiO3 to further improve the photocatalytic property.

Microrobots driven by multiple propelling forces hold great potential for noninvasively targeted delivery in the physiologic environment. However, the remotely collective perception and precise propelling in a low Reynold’s number bioenvironment remain the major challenges of microrobots to achieve desired therapeutic effects in vivo. Here, we reported a biohybrid microrobot that integrated with magnetic, thermal, and hypoxia sensitivities and an internal fluorescent protein as the dual reporter of thermal and positioning signals for targeted cancer treatment. There were three key elements in the microrobotic system, including the magnetic nanoparticle (MNP)-loaded probiotic Escherichia coli Nissle1917 (EcN@MNP) for spatially magnetic and hypoxia perception, a thermal-logic circuit engineered into the bacteria to control the biosynthesis of mCherry as the temperature and positioning reporter, and NDH-2 enzyme encoded in the EcN for enhanced anticancer therapy. According to the fluorescent-protein-based imaging feedback, the microrobot showed good thermal sensitivity and active targeting ability to the tumor area in a collective manner under the magnetic field. The cancer cell apoptosis was efficiently triggered in vitro and in vivo by the hybrid microrobot coupled with the effects of magnetothermal ablation and NDH-2-induced reactive oxygen species (ROS) damage. Our study demonstrates that the biohybrid EcN microrobot is an ideal platform to integrate the physical, biological, and chemical properties for collective perception and propelling in targeted cancer treatment.

In cells, mechanical forces play a key role in impacting cell behaviors, including adhesion, differentiation, migration, and death. Herein, a 20 nm mitochondria‐targeted zinc‐doped iron oxide nanocube is designed as a nanospinner to exert mechanical forces under a rotating magnetic field (RMF) at 15 Hz and 40 mT to fight against cancer. The nanospinners can efficiently target the mitochondria of cancer cells. By means of the RMF, the nanocubes assemble in alignment with the external field and produce a localized mechanical force to impair the cancer cells. Both in vitro and in vivo studies show that the nanospinners can damage the cancer cells and reduce the brain tumor growth rate after the application of the RMF. This nanoplatform provides an effective magnetomechanical approach to treat deep‐seated tumors in a spatiotemporal fashion.

Remote control of cells and the regulation of cell events at the molecular level are of great interest in the biomedical field. In addition to chemical compounds and genes, mechanical forces play a pivotal role in regulating cell fate, which have prompted the rapid growth of mechanobiology. From a perspective of nanotechnology, magnetic nanomaterials (MNs) are an appealing option for mechanotransduction due to their capabilities in spatiotemporal manipulation of mechanical forces via the magnetic field. As a newly developed paradigm, magneto-mechanotransduction is harnessed to physically regulate cell fate for biomedical applications. Here, the critical factors that determine the magnetomechanical forces induced by MNs in mechanotransduction are briefly reviewed. Recent innovative approaches and their underlying mechanisms for controlling cell fate are highlighted, which offer possibilities for the remote mechanical manipulation of cells and biomolecules in a precise manner. Promising applications including regenerative medicine and cancer treatment based on magnetomechanical stimulation through MNs are also addressed. Perspectives and challenges in MN-based mechanotransduction are commented.

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