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Unlike conventional 1H magnetic resonance imaging (MRI), 19F MRI features unambiguous detection of fluorine spins due to negligible background signals. Therefore, it is considered a promising noninvasive and selective imaging method for the diagnosis of cancers and other diseases. For 19F MRI, fluorine-rich molecules such as perfluorocarbons (PFC) have been formulated into nanoemulsions and used as its tracer agent. Along with advancements in other types of nanoparticles as targeted theranostics and stimuli-triggered probes and combined with the advantages of 19F MRI, PFC nanoemulsions are being empowered with these additional functionalities and becoming a promising theranostic platform. In this Review, we provide an overview of fluorine-based materials for sensitive 19F MRI of biological and pathological conditions. In particular, we describe designs and applications of recently reported stimuli-responsive and theranostic 19F MRI probes. Finally, challenges and future perspectives regarding the further development of 19F MRI probes for their clinical applications are described.

Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, which is associated with metastatic potential and poor prognosis in cancer patients. Therefore, development of EGFR-targeted sensitive imaging probes has been a challenge in tumor targeting, image-guided cancer surgery, patient-selective anti-EGFR therapy, and efficient targeted therapies. Methods: We synthesized a zwitterionic near-infrared fluorophore (ATTO655)-conjugated epidermal growth factor (EGF) as a novel activatable molecular probe. Fluorescence OFF/ON property and EGFR-targeting specificity of EGF-ATTO655 as well as its utility in real-time near-infrared (NIR) fluorescence imaging of EGFR-positive cancers were evaluated using in vitro and in vivo studies. Results: When conjugated to EGF, the fluorescence of ATTO655 quenched efficiently by photo-induced electron transfer (PET) mechanism between the conjugated dyes and nearby amino acid quenchers (tryptophan/tyrosine residues), which was stably maintained at physiological pH and in the presence of serum for at least 17 h. The fluorescence of EGF-ATTO655 turned on by receptor-mediated endocytosis and subsequent disintegration of EGF in EGFR-positive A431 cancer cells, thereby enabling specific and real-time fluorescence imaging of EGFR-positive cancer cells. Consequently, EGFR-positive tumors could be clearly visualized 3 h post-injection with a significantly high tumor-to-background ratio (TBR = 6.37). Conclusion: This PET mechanism-based OFF/ON type of EGF probe showed great potential for rapid, real-time, and target-cell-specific imaging of EGFR-overexpressing cancers in vitro and in vivo.

Radiotherapy (RT) is a major modality for cancer treatment, along with surgery and chemotherapy. Despite its therapeutic effect, the recurrence and metastasis of tumors due to the acquired resistance of cancer cells to RT remain significant clinical problems. Therefore, it is imperative to overcome radioresistance and improve radiosensitivity in cancer patients. Here, we synthesized hydroxychloroquine (HCQ)-loaded hollow mesoporous silica nanoparticles (HMSNs) to enable effective inhibition of radiation-induced cytoprotective autophagy and enhance the therapeutic efficacy of RT. HCQ-HMSN-treated HCT116 colon cancer cells showed a 200-fold higher intracellular uptake of HCQ than that of free HCQ-treated cells, thereby effectively inhibiting the radiation-induced autophagy of cancer cells. In vivo imaging and therapy studies of a tumor xenograft model showed preferential accumulation of HCQ-HMSNs in tumor tissues and significant enhancement of RT by inhibiting autophagy in the tumor sites. Histopathology analyses of major organs, blood chemistry profiles, and changes in body weights of mice confirmed the good biocompatibility of HCQ-HMSNs.

The AP2/EREBP family transcription factors play important roles in a wide range of stress tolerance and hormone signaling. In this study, a heat-inducible rice ERF gene was isolated and functionally characterized. The OsERF115/AP2EREBP110 was categorized to Group-IIIc of the rice AP2/EREBP family and strongly induced by heat and drought treatment. The OsERF115/AP2EREBP110 protein targeted to nuclei and suppressed the ABA-induced transcriptional activation of Rab16A promoter in rice protoplasts. Overexpression of OsERF115/AP2EREBP110 enhanced thermotolerance of seeds and vegetative growth stage plants. The OsERF115/AP2EREBP110 overexpressing (OE) plants exhibited higher proline level and increased expression of a proline biosynthesis P5CS1 gene. Phenotyping of water use dynamics of the individual plant indicates that the OsERF115/AP2EREBP110-OE plant exhibited better water saving traits under heat and drought combined stress. Our combined results suggest the potential use of OsERF115/AP2EREBP110 as a candidate gene for genetic engineering approaches to develop heat and drought stress-tolerant crops.

Multidrug resistance (MDR) is a leading cause of failure in current chemotherapy treatment and constitutes a formidable challenge in therapeutics. Here, we demonstrate that a nanoscale magnetic tandem apoptosis trigger (m-TAT), which consists of a magnetic nanoparticle and chemodrug (e.g., doxorubicin), can completely remove MDR cancer cells in both in vitro and in vivo systems. m-TAT simultaneously activates extrinsic and intrinsic apoptosis signals in a synergistic fashion and downregulates the drug efflux pump (e.g., P-glycoprotein) which is one of the main causes of MDR. The tandem apoptosis strategy uses low level of chemodrug (in the nanomolar (nM) range) to eliminate MDR cancer cells. We further demonstrate that apoptosis of MDR cancer cells can be achieved in a spatially selective manner with single-cell level precision. Our study indicates that nanoscale tandem activation of convergent signaling pathways is a new platform concept to overcome MDR with high efficacy and specificity.

Unlike conventional

Nanomaterials have revolutionized cancer imaging, diagnosis, and treatment. Multifunctional nanoparticles in particular have been designed for targeted cancer therapy by modulating their physicochemical properties to be delivered to the target and activated by internal and/or external stimuli. This review will focus on the fundamental “chemical” design considerations of stimuli-responsive nanosystems to achieve favorable tumor targeting beyond biological barriers and, furthermore, enhance targeted cancer therapy. In addition, we will summarize innovative smart nanosystems responsive to external stimuli (e.g., light, magnetic field, ultrasound, and electric field) and internal stimuli in the tumor microenvironment (e.g., pH, enzyme, redox potential, and oxidative stress).

Cell-based therapies are attractive for treating various degenerative disorders and cancer but delivering functional cells to the region of interest in vivo remains difficult. The problem is exacerbated in dense biological matrices such as solid tissues because these environments impose significant steric hindrances for cell movement. Here, we show that neural stem cells transfected with zinc-doped ferrite magnetic nanoparticles (ZnMNPs) can be pulled by an external magnet to migrate to the desired location in the brain. These magnetically labeled cells (Mag-Cells) can migrate because ZnMNPs generate sufficiently strong mechanical forces to overcome steric hindrances in the brain tissues. Once at the site of lesion, Mag-Cells show enhanced neuronal differentiation and greater secretion of neurotrophic factors than unlabeled control stem cells. Our study shows that ZnMNPs activate zinc-mediated Wnt signaling to facilitate neuronal differentiation. When implemented in a rodent brain stroke model, Mag-Cells led to significant recovery of locomotor performance in the impaired limbs of the animals. Our findings provide a simple magnetic method for controlling migration of stem cells with high therapeutic functions, offering a valuable tool for other cell-based therapies.

In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs) stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid) and analyzed their effect on non-small cell lung cancer (NSCLC) cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH)-responsive dissolution and subsequent enhancement in magnetic resonance (MR) imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.

The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles (Zn(0.4)Fe(2.6)O(4)), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.

Mesoporous silica nanoparticles are useful nanomaterials that have demonstrated the ability to contain and release cargos with mediation by gatekeepers. Magnetic nanocrystals have the ability to exhibit hyperthermic effects when placed in an oscillating magnetic field. In a system combining these two materials and a thermally sensitive gatekeeper, a unique drug delivery system can be produced. A novel material that incorporates zinc-doped iron oxide nanocrystals within a mesoporous silica framework that has been surface-modified with pseudorotaxanes is described. Upon application of an AC magnetic field, the nanocrystals generate local internal heating, causing the molecular machines to disassemble and allowing the cargos (drugs) to be released. When breast cancer cells (MDA-MB-231) were treated with doxorubicin-loaded particles and exposed to an AC field, cell death occurred. This material promises to be a noninvasive, externally controlled drug delivery system with cancer-killing properties.