Currently, the potential of cancer therapy is compromised by a variety of problems related to tumor specificity, drug access, and limited efficacy. We report a novel approach to improve the effectiveness of cancer treatment utilizing a light-responsive nanoconstruct. Effectiveness is increased by enhancing drug absorption through heating and the production of free radicals. Treatment specificity is increased through chemical targeting of the nanoconstruct and localization of light delivery to the tumor. When reaching the tumor, magnetic resonance imaging is enhanced and near-infrared fluorescence is activated upon drug release, making it possible to visualize the localized treatment at both the tissue and cellular levels. This dual-modality imaging nanoconstruct enables the synergistic treatment and observable evaluation of solid tumors with dramatically improved efficacy, giving rise to a promising new approach for cancer therapy and evaluation.Keywords: biological redox therapy; dual-modality imaging; graphene quantum dots; photodynamic therapy; photothermal therapy;

Biothiols such as gluthathione (GSH), cysteine (Cys), homocysteine (Hcy), and thioredoxin (Trx) play vital roles in cellular metabolism. Various diseases are associated with abnormal cellular biothiol levels. Thus, the intracellular detection of biothiol levels could be a useful diagnostic tool. A number of methods have been developed to detect intracellular thiols, but sensitivity and specificity problems have limited their applications. To address these limitations, we have designed a new biosensor based on hyperpolarized xenon magnetic resonance detection, which can be used to detect biothiol levels noninvasively. The biosensor is a multimodal probe that incorporates a cryptophane-A cage as 129Xe NMR reporter, a naphthalimide moiety as fluorescence reporter, a disulfide bond as thiol-specific cleavable group, and a triphenylphosphonium moiety as mitochondria targeting unit. When the biosensor interacts with biothiols, disulfide bond cleavage leads to enhancements in the fluorescence intensity and changes in the 129Xe chemical shift. Using Hyper-CEST (chemical exchange saturation transfer) NMR, our biosensor shows a low detection limit at picomolar (10–10 M) concentration, which makes a promise to detect thiols in cells. The biosensor can detect biothiol effectively in live cells and shows good targeting ability to the mitochondria. This new approach not only offers a practical technique to detect thiols in live cells, but may also present an excellent in vivo test platform for xenon biosensors.

Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) play an important role in regulating the vital functions of living organisms. Knowledge of their biodistribution in real-time could help diagnose a variety of conditions. However, existing methods of biothiol detection are invasive and require assays. Herein we report a molecular biosensor for biothiol detection using the nuclear spin resonance of 129Xe. The 129Xe biosensor consists of a cryptophane cage encapsulating a xenon atom and an acrylate group. The latter serves as a reactive site to covalently bond biothiols through a thiol-addition reaction. The biosensor enables discrimination of Cys from Hcy and GSH through the chemical shift and average reaction rate. This biosensor can be detected at a concentration of 10 μM in a single scan and it has been applied to detect biothiols in bovine serum solution. Our results indicate that this biosensor is a promising tool for the real-time imaging of biothiol distributions.

Real-time diagnosis and monitoring of disease development, and therapeutic responses to treatment, are possible by theranostic magnetic resonance imaging (MRI). Here we report the synthesis of a multifunctional liposome, which contains Gd-DOTA (an MRI probe), paclitaxel and c(RGDyk) (a targeted peptide). This nanoparticle overcame the insolubility of paclitaxel, reduced the side effects of FDA-approved formulation of PTX-Cre (Taxol®) and improved drug delivery efficiency to the tumor. c(RGDyk) modification greatly enhanced the cytotoxicity of the drug in tumor cells A549. The T1 relaxivity in tumor cells treated with the targeted liposome formulation was increased 16-fold when compared with the non-targeted group. In vivo, the tumors in mice were visualized using T1-weighted imaging after administration of the liposome. Also the tumor growth could be inhibited well after the treatment. Fluorescence images in vitro and ex vivo also showed the targeting effect of this liposome in tumor cells, indicating that this nanovehicle could limit the off-target side effects of anticancer drugs and contrast agents. These findings lay the foundation for further tumor inhibition study and application of this delivery vehicle in cancer therapy settings.

A novel thermo-sensitive micelle contrast agent and its enhancement of MRI contrast with temperature are reported. The morphology changes sharply near 37 °C, resulting in a significant amplification of the CEST signal. This enables detection of small changes in body temperature.

A novel reconstituted high-density lipoprotein (rHDL) nanocomposite has been prepared for highly-sensitive magnetic resonance (MR)-fluorescence multimodal imaging. Such a nanocomposite is able to enhance the MR sensitivity up to 129 fold in comparison to the traditional small molecule MRI agent based on paramagnetic chemical exchange saturation transfer (PARACEST). It has also demonstrated specific targeting to macrophage cells, which shows great potential for the detection of atherosclerosis.

Novel pH-triggered nanoprobe were fabricated for 19F MRI and fluorescence imaging (MRI-FI) of cancer cells. The biocompatibility, durability, high internalizing efficiency and pore architecture justify the Au-fluorescent mesoporous silica nanoparticles as ideal, highly sensitive and highly specific vectors for 19F MRI and FI of cancer cells.

•Ultrahigh NMR signal sensitivity: Utilization of hyperpolarized Xe NMR, which enhances the signal more than 10,000 times over the conventional NMR at thermal equilibrium.•Large chemical shift response: Novelty designed supermolecule sensor enables 129Xe NMR spectroscopy was shifted up to 6.4 ppm in the presence of Zn2+ ions, which is 4 times larger than that of the reported similar sensor.•High selectivity to Zn2+ions: The response of Xe NMR exhibited high selectivity to Zn2+ ions as discriminated from other six potentially competing metal ions.•Fast and non-destructive analytical techniques: Take the advantage of NMR technique, the determination of Zn2+ ions was allowed in solution and in solid state, as well as to enable the study of biological tissues.Although Zn2+ ions are involved in large numbers of physiopathological processes, non-invasive detection of Zn2+ ions in opaque biological samples remains a huge challenge. Here, we developed a novel zinc-responsive hyperpolarized (HP) 129Xe-based NMR molecular sensor. This HP 129Xe-based NMR molecular sensor was synthesized by attaching 2-(diphenylphosphino) benzenamine as ligand for zinc ions to the xenon-binding supramolecular cage, cryptophane. The 129Xe NMR spectroscopy of such molecular sensor was shifted up to 6.4 ppm in the presence of Zn2+ ions, which was nearly four times larger than that of the reported similar sensor. The application of the sensor would benefit low concentration detection by using indirect NMR/MRI method. The response exhibited high sensitivity and selectivity as discriminated from other six potentially competing metal ions. The application of this sensor in the analysis of zinc ions in the rat serum samples was also evaluated. The strategy is generally applicable in developing sensitive and selective sensors for quantitative determination of zinc ions.We developed a novel hyperpolarized 129Xe-based NMR molecular sensor for detection of Zn2+ ions. The 129Xe NMR spectroscopy of such molecular sensor was shifted up to 6.4 ppm in the presence of Zn2+ ions, which was nearly four times larger than that of the reported similar sensor. This zinc-activated HP 129Xe-based NMR molecular sensor suggests a great potential to be used in the monitoring of Zn2+ ions and investigating Zn2+ ions related physiopathological processes in biological organisms in the foreseeable future.

•We present an adaptive entropy-based window selection scheme.•The novel local difference measure map can keep low false alarm rates under the same probability of detection.•The proposed method is simple and effective with regard to detection accuracy.Dim and small target detection in complex background is considered a difficult and challenging problem. Conventional algorithms using the local difference/mutation possibly produce high missed or mistaken detection rates. In this paper, we propose an effective algorithm for detecting dim and small infrared targets. In order to synchronously enhance targets and suppress complex background clutters, we adopt an adaptive entropy-based window selection technique to construct a novel local difference measure (LDM) map of an input image, which measures the dissimilarity between the current region and its neighboring ones. In this way, the window size can be adaptively regulated according to local statistical properties. Compared with the original image, the LDM map has less background clutters and noise residual. This guarantees the lower false alarm rates under the same probability of detection. Subsequently, a simple threshold is used to segment the target. More than 600 dim and small infrared target images against different complex and noisy backgrounds were utilized to validate the detection performance of the proposed approach. Extensive experimental results demonstrate that the proposed method not only works more stably for different target movements and signal-to-clutter ratio values, but also has a better performance compared with classical baseline methods. The evaluation results suggest that the proposed method is simple and effective with regard to detection accuracy.

A novel thermo-sensitive micelle contrast agent and its enhancement of MRI contrast with temperature are reported. The morphology changes sharply near 37 °C, resulting in a significant amplification of the CEST signal. This enables detection of small changes in body temperature.

Novel pH-triggered nanoprobe were fabricated for 19F MRI and fluorescence imaging (MRI-FI) of cancer cells. The biocompatibility, durability, high internalizing efficiency and pore architecture justify the Au-fluorescent mesoporous silica nanoparticles as ideal, highly sensitive and highly specific vectors for 19F MRI and FI of cancer cells.