New‐era soft microrobots for biomedical applications need to mimic the essential structures and collective functions of creatures from nature. Biocompatible interfaces, intelligent functionalities, and precise locomotion control in a collective manner are the key parameters to design soft microrobots for the complex bio‐environment. In this work, a biomimetic magnetic microrobot (BMM) inspired by magnetotactic bacteria (MTB) with speedy motion response and accurate positioning is developed for targeted thrombolysis. Similar to the magnetosome structure in MTB, the BMM is composed of aligned iron oxide nanoparticle (MNP) chains embedded in a non‐swelling microgel shell. Linear chains in BMMs are achieved due to the interparticle dipolar interactions of MNPs under a static magnetic field. Simulation results show that, the degree and speed of assembly is proportional to the field strength. The BMM achieves the maximum speed of 161.7 µm s−1 and accurate positioning control under a rotating magnetic field with less than 4% deviation. Importantly, the locomotion analyses of BMMs demonstrate the frequency‐dependent synchronization under 8 Hz and asynchronization at higher frequencies due to the increased drag torque. The BMMs can deliver and release thrombolytic drugs via magneto‐collective control, which is promising for ultra‐minimal invasive thrombolysis.

Targeted therapy is highly challenging and urgently needed for patients diagnosed with triple negative breast cancer (TNBC). Here, a synergistic treatment platform with plasmonic–magnetic hybrid nanoparticle (lipids, doxorubicin (DOX), gold nanorods, iron oxide nanocluster (LDGI))–loaded mesenchymal stem cells (MSCs) for photoacoustic imaging, targeted photothermal therapy, and chemotherapy for TNBC is developed. LDGI can be efficiently taken up into the stem cells with good biocompatibility to maintain the cellular functions. In addition, CXCR4 on the MSCs is upregulated by iron oxide nanoparticles in the LDGI. Importantly, the drug release and photothermal therapy can be simultaneously achieved upon light irradiation. The released drug can enter the cell nucleus and promote cell apoptosis. Interestingly, light irradiation can control the secretion of cellular microvehicles carrying LDGI for targeted treatment. A remarkable in vitro anticancer effect is observed in MDA‐MB‐231 with near‐infrared laser irradiation. In vivo studies show that the MSCs‐LDGI has the enhanced migration and penetration abilities in the tumor area via both intratumoral and intravenous injection approaches compared with LDGI. Subsequently, MSCs‐LDGI shows the best antitumor efficacy via chemo‐photothermal therapy compared to other treatment groups in the TNBC model of nude mice. Thus, MSCs‐LDGI multifunctional system represents greatly synergistic potential for cancer treatment.

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.

Targeting activated macrophages using anti-inflammatory phytopharmaceuticals has been proposed as general therapeutic approaches for rheumatic diseases. Besides macrophages, chondrocytes are another promising target of anti-inflammatory agents. Tetrandrine is a major bisbenzylisoquinoline alkaloid isolated from Stephania tetrandrae S. Moore which has been used for 2,000 years as an antirheumatic herbal drug in China. Although, the anti-inflammatory effect of tetrandrine has been demonstrated, the mechanism has not been clearly clarified. In this study, we designed a comprehensive anti-inflammatory evaluation system for tetrandrine, including complete Freund's adjuvant (CFA)-induced arthritis rat, LPS-induced macrophage RAW 264.7 cells, and chondrogenic ATDC5 cells. The results showed that tetrandrine alleviated CFA-induced foot swelling, synovial inflammation, and proinflammatory cytokines secretion. Tetrandrine could inhibit IL-6, IL-1b, and TNF-a expression via blocking the nuclear translocation of nuclear factor (NF)-kB p65 in LPS-induced RAW 264.7 cells. Moreover, ATDC5 cells well responded to LPS induced proinflammatory mediators secretion and tissue degradation, and tetrandrine could also inhibit the production of nitric oxide and prostaglandin E 2 , as well as the expression of matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 via inhibiting IkBa phosphorylation and degradation. In conclusion, the results showed that one of the anti-inflammatory mechanisms of tetrandrine was inhibiting IkBa and NF-kB p65 phosphorylation in LPS-induced macrophage RAW 264.7 cells and chondrogenic ATDC5 cells. Moreover, we introduce a vigorous in vitro cell screening system, LPS-induced murine macrophage RAW 264.7 cells coupling chondrogenic ADTC5 cells, for screening anti-rheumatic drugs. ß

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment.

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.

Targeted delivery of nanomedicines into the tumor site and improving the intratumoral distribution remain challenging in cancer treatment. Here, we report an effective transportation system utilizing both of mesenchymal stem cells (MSCs) and their secreted microvesicles containing assembled gold nanostars (GNS) for targeted photothermal therapy of prostate cancer. The stem cells act as a cell carrier to actively load and assemble GNS into the lysosomes. Accumulation of GNS in the lysosomes facilitates the close interaction of nanoparticles, which could result in a 20 nm red-shift of surface plasmon resonance of GNS with a broad absorption in the near infrared region. Moreover, the MSCs can behave like an engineering factory to pack and release the GNS clusters into microvesicles. The secretion of GNS can be stimulated via light irradiation, providing an external trigger-assisted approach to encapsulate nanoparticles into cell derived microvesicles. In vivo studies demonstrate that GNS-loaded MSCs have an extensive intratumoral distribution, as monitored via photoacoustic imaging, and efficient antitumor effect under light exposure in a prostate-cancer subcutaneous model by intratumoral and intravenous injection. Our work presents a light-responsive transportation approach for GNS in combination of MSCs and their extracellular microvesicles and holds the promise as an effective strategy for targeted cancer therapy including prostate cancer.

Developing a spatiotemporal-controlled platform with feasible synthesis and multifunctionality is highly desirable in the field of nanomedicine. Here, we present a near-infrared (NIR)-light-triggered approach to control the supramolecular assembly system for drug release and achieve synergistic chemo-photothermal therapy for cancer. A cucurbit[7]uril (CB[7]) stabilized gold nanostar (GNS) platform is designed to encapsulate the anticancer drug camptothecin (CPT) via host-guest chemistry. Importantly, CB[7] behaves not only as a surfactant to improve the stability of GNS in the aqueous solution but also as the cage for intermolecular assembly of CPT molecules. Moreover, without the competitive complexation, the drug release could be stimulated under NIR light irradiation. Synergistic treatment of cancer can be achieved by combining chemotherapy with the photothermal effect of GNS. This work develops a NIR-light-triggered cucurbituril-based drug-release approach that opens the door for remote control of drug release in the supramolecular assembly system.