AbstractNeutrophils can responsively release reactive oxygen species (ROS) to actively combat infections by exogenous stimulus and cascade enzyme catalyzed bio‐oxidation. A supramolecular nanogel is now used as an artificial neutrophil by enzymatic interfacial self‐assembly of peptides (Fmoc‐Tyr(H2PO3)‐OH) with magnetic nanoparticles (MNPs) and electrostatic loading of chloroperoxidase (CPO). The MNPs within the nanogel can elevate H2O2 levels in cancer cells under programmed alternating magnetic field (AMF) similar to the neutrophil activator, and the loaded CPO within protective peptides nanolayer converts the H2O2 into singlet oxygen (1O2) in a sustained manner for neutrophil‐inspired tumor therapy. As a proof of concept study, both the H2O2 and 1O2 in cancer cells increase stepwise under a programmed alternating magnetic field. An active enzyme dynamic therapy by magnetically stimulated oxygen stress and sustained enzyme bio‐oxidation is thus shown with studies on both cells and animals.

The targeted delivery of nanomedicines into solid tumors remains challenging in cancer treatment. Stem cells with tumortropic migration ability are promising as biocarriers to transport nanomedicines. The transportation of nanomedicines into cancer cells is the key step for tumor targeted delivery via stem cells. In this study, we designed a magnetic nanocube (scMNP) loaded in mesenchymal stem cells for magnetic hyperthermia of prostate cancer, and the delivery and transportation pathways into the cancer cells were fully investigated. The MSCs acted as the carrier of the loaded scMNPs along with the upregulation of CXCR4 for the migration to cancer cells. The therapeutic effect was mainly due to scMNPs via magnetic hyperthermia. Stem cell-derived microvesicles containing scMNPs played an essential role in the crosstalk between stem cells and cancer cells for targeted delivery. Both in vitro and in vivo studies demonstrated that the system showed satisfactory therapeutic efficiency under magnetic hyperthermia therapy. Our investigation presents a comprehensive study of magnetic nanoparticles in combination with MSCs and their extracellular microvesicles and is promising as an effective strategy for magnetic hyperthermia therapy of prostate cancer.

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.

BACKGROUND:Therapeutic applications of stem cells, especially mesenchymal stem cells, were once regarded as a promising therapy for mitigating acute cerebral infarction. Unfortunately, all the stem cell clinical trials have been futile. A new stroke therapeutic strategy of combining stem cells with nanotechnology has recently gained significant attention. The objective of this study was to evaluate the application of cerium oxide nanoparticle (nanoceria)-labeled human umbilical cord mesenchymal stem cells (HucMSCs) for stroke therapy.METHODS:In our study, cerium oxide nanoparticles were precovered with hyaluronic acid before labeling HucMSCs and the synergistic effects from both HucMSCs and cerium oxide nanoparticles were analyzed in in vivo and in vitro experiments.RESULTS:The nanoceria-labeled HucMSCs combined advantages from both sides, including the capacity for inflammatory modulation of HucMSCs and the antioxidant effects of nanoceria. Compared with either HucMSCs or nanoceria individually, nanoceria-labeled HucMSCs exerted significantly enhanced capacities after gaining combined antioxidant and anti-inflammatory effects.CONCLUSION:Our findings suggest a novel strategy with effective and well-tolerated applications of stem cells for acute cerebral infarction therapy after modification of cells with nanomaterials.

The peroxidase-like functionality of iron oxide (IO) nanoparticles has attracted substantial attention in cancer treatment by reactive oxygen species (ROS) catalytic over-generation. However, the inefficient intracellular ROS generation still hurdles ready-to-use application of IO nanoparticles, attributing to the transient lifetime and limited diffusion distance of ROS. Indeed, excessive ROS generation in mitochondria is desirable to enhance cell death against cancer cells. In this study, we designed zinc-doped magnetic nanoparticles (MNPs) conjugated with triphenylphosphonium (TPP) for mitochondrial targeting. Moreover, the nanoparticles with high absorbance in visible region can catalyze ROS overproduction under visible light irradiation. Our platform provides a novel application of MNPs in targeted cancer therapy, which serves as a light-controlled switch to accelerate ROS generation and induce incremental cellular death.

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.

We designed and explored self-assembled gold nanoparticles (SAGNPs) by introducing dithiol modified polyethylene glycol (PEG) for internanoparticle cross-linking. SAGNPs could enhance uptake into cancer cells and be disintegrated by glutathione (GSH) to achieve tumor microenvironment-activated biodegradation. This assembled structure improved the photothermal effect compared to single gold nanospheres.

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.

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.

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.