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Inspired by the tactic organisms in Nature that can self-direct their movement following environmental stimulus gradient, we proposed a DNase functionalized Janus nanoparticle (JNP) nanomotor system for the first time, which can be powered by ultralow nM to μM levels of DNA. The system exhibited interesting chemotactic behavior toward a DNA richer area, which is physiologically related with many diseases including tumors. In the presence of the subtle DNA gradient generated by apoptotic tumor cells, the cargo loaded nanomotors were able to sense the DNA signal released by the cells and demonstrate directional motion toward tumor cells. For our system, the subtle DNA gradient by a small amount (10 μL) of tumor cells is sufficient to induce the chemotaxis behavior of self-navigating and self-targeting ability of our nanomotor system, which promises to shed new light for tumor diagnosis and therapy.

Cancer vaccines play a key role in the prevention and treatment of early and recurrent tumors. Although they have been widely studied during the past few decades, designing an efficient and economical cancer vaccine is still challenging. Here, we propose an injectable live cell cancer vaccine (InLCCV) using live tumor cells as immunogenic sources for cancer immunoprophylaxis and immunotherapy. InLCCV is fabricated by loading live mouse breast cancer cells (4T1 cells), gold nanorods (GNRs), and super-low-dose lipopolysaccharide (LPS) into a biocompatible Pluronic F127 in situhydrogel matrix. After in situinactivation by the photothermal effect of GNRs upon near-infrared (NIR) laser irradiation, immunogenic cell death (ICD) of 4T1 cells is induced and tumor-associated antigens (TAAs) together with loaded LPS are released subsequently. Therefore, dendritic cells and macrophages are activated accordingly, further stimulating the systemic anti-tumor immune response. After vaccinating with InLCCV, the tumor-free percentage of the mice is 60% and the survival rate during the observation period reaches up to 80%. For lung metastasis, the metastatic foci are 3.9-fold less than those of the control group. The as-developed InLCCV shows much promise as a potential platform for breast cancer immunoprophylaxis and immunotherapy.

Cancer remains a primary threat to human lives. Recently, amplification of tumor-associated reactive oxygen species (ROS) has been used as a boosting strategy to improve tumor therapy. Here, we report on a bone-targeting prodrug mesoporous silica-based nanoreactor for combined photodynamic therapy (PDT) and enhanced chemotherapy for osteosarcoma. Because of surface modification of a bone-targeting biphosphate moiety and the enhanced permeability and retention effect, the formed nanoreactor shows efficient accumulation in osteosarcoma and exhibits long-term retention in the tumor microenvironment. Upon laser irradiation, the loaded photosensitizer chlorin e6 (Ce6) produces in situ ROS, which not only works for PDT but also functions as a trigger for controlled release of doxorubicin (DOX) and doxycycline (DOXY) from the prodrugs based on a thioketal (TK) linkage. The released DOXY further promotes ROS production, thus perpetuating subsequent DOX/DOXY release and ROS burst. The ROS amplification induces long-term high oxidative stress, which increases the sensitivity of the osteosarcoma to chemotherapy, therefore resulting in enhanced tumor cell inhibition and apoptosis. The as-developed nanoreactor with combined PDT and enhanced chemotherapy based on ROS amplification shows significant promise as a potential platform for cancer treatment.

Microrobot assembled by magnetic nanoparticles was developed as a novel mechanical signal generator for precise macrophage polarization. Theoretical and experimental demonstrations not only revealed the magneto‐driven principles of microrobots, but also probed their ability for successful macrophage polarization via fixed‐point rotational motion, opening a new avenue for mechanical regulation of cell fate.

The importance of mechanical signals in regulating the fate of macrophages is gaining increased attention recently. However, the recently used mechanical signals normally rely on the physical characteristics of matrix with non‐specificity and instability or mechanical loading devices with uncontrollability and complexity. Herein, we demonstrate the successful fabrication of self‐assembled microrobots (SMRs) based on magnetic nanoparticles as local mechanical signal generators for precise macrophage polarization. Under a rotating magnetic field (RMF), the propulsion of SMRs occurs due to the elastic deformation via magnetic force and hydrodynamics. SMRs perform wireless navigation toward the targeted macrophage in a controllable manner and subsequently rotate around the cell for mechanical signal generation. Macrophages are eventually polarized from M0 to anti‐inflammatory related M2 phenotypes by blocking the Piezo1‐activating protein‐1 (AP‐1）‐CCL2 signaling pathway. The as‐developed microrobot system provides a new platform of mechanical signal loading for macrophage polarization, which holds great potential for precise regulation of cell fate.‐ This work describes a novel approach for macrophage polarization utilizing microrobots assembled by magnetic nanoparticles. It not only probed their system for macrophage polarization but also provided an excellent theoretical and experimental demonstration of the magneto‐driven principles of their chain microrobots.

Various strategies have been designed for myotube contraction and skeletal muscle stimulation in recent years, aiming in the field of skeletal muscle tissue engineering and bionics. However, most of the current approaches lack controllability and adaptability for precise stimulation, especially at the microlevel. Herein, wireless and precise activation of muscle by using magnetic biohybrid microswimmers in combination with near-infrared (NIR) laser irradiation is successfully demonstrated. Biohybrid microswimmers are fabricated by dip-coating superparamagnetic Fe3O4nanoparticles onto the chlorellamicroalgae, thus endowing robust navigation in various biological media due to magnetic actuation. Under the guidance of a rotating magnetic field, the engineered microswimmer can achieve precise motion toward a single C2C12-derived myotube. Upon NIR irradiation, the photothermal effect from the incorporated Fe3O4nanoparticles results in local temperature increments of approximately 5 °C in the targeted myotube, which could efficiently trigger the contraction of myotube. The mechanism underlying this phenomenon is a Ca2+-independent case involving direct actin–myosin interactions. In vivomuscle fiber contraction and histological test further demonstrate the effectiveness and biosafety of our design. The as-developed biohybrid microswimmer-based strategy is possible to provide a renovation for tissue engineering and bionics.

Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2nanoparticles with catalytic activity for active Fenton-like Mn2+delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.

Inducing neural stem cells to differentiate and replace degenerated functional neurons represents the most promising approach for neural degenerative diseases including Parkinson’s disease, Alzheimer’s disease, etc. While diverse strategies have been proposed in recent years, most of these are hindered due to uncontrollable cell fate and device invasiveness. Here, we report a minimally invasive micromotor platform with biodegradable helical Spirulina plantensis(S. platensis) as the framework and superparamagnetic Fe3O4nanoparticles/piezoelectric BaTiO3nanoparticles as the built-in function units. With a low-strength rotational magnetic field, this integrated micromotor system can perform precise navigation in biofluid and achieve single-neural stem cell targeting. Remarkably, by tuning ultrasound intensity, thus the local electrical output by the motor, directed differentiation of the neural stem cell into astrocytes, functional neurons (dopamine neurons, cholinergic neurons), and oligodendrocytes, can be achieved. This micromotor platform can serve as a highly controllable wireless tool for bioelectronics and neuronal regenerative therapy.