Wenbin Zeng

Dye Loaded Ferritin Nanocages for Multimodal Imaging and Photothermal Therapy

Multimodal imaging-guided photothermal therapy (PTT), for the therapy of cancer, based on a ferritin (FRT) nanocage loaded with the near-infrared dye IR820 (designated DFRT) is demonstrated. The dual roles of DFRT (in imaging and PTT) are successfully balanced by using two different excitation wavelengths: 550 nm for high quantum-yield fluorescence imaging on the one hand and 808 nm for photoacoustic imaging and PTT with high photothermal conversion efficiency on the other.

Molecular Imaging of Apoptosis: From Micro to Macro

Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus.

Dual-Modality Noninvasive Mapping of Sentinel Lymph Node by Photoacoustic and Near-Infrared Fluorescent Imaging Using Dye-Loaded Mesoporous Silica Nanoparticles.

The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we developed an imaging contrast system based on fluorescent dye-loaded mesoporous silica nanoparticles (MSNPs) that integrate near-infrared (NIR) fluorescent and photoacoustic (PA) imaging modalities for efficient SLN mapping. By balancing the ratio of dye and nanoparticles for simultaneous optimization of dual-modality imaging (NIR and PA), the dye encapsulated MSNP platform was set up to generate both a moderate NIR emission and PA signals simultaneously. Moreover, the underlying mechanisms of the relevance between optical and PA properties were discovered. Subsequently, dual-modality imaging was achieved to visualize tumor draining SLNs up to 2 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate and contrast between metastatic and normal SLNs were observed both in vivo and ex vivo. Based on all these imaging data, it was demonstrated that the dye-loaded MSNPs allow detection of regional lymph nodes in vivo with time-domain NIR fluorescent and PA imaging methods efficiently.

A novel upconversion luminescence turn-on nanosensor for ratiometric detection of organophosphorus pesticides

In this paper, an upconversion luminescence (UCL) “turn-on” nanosensor based on Tween-20 modified blue-emissive upconversion nanoparticles (UCNPs) has been fabricated for the ratiometric detection of organophosphorus (OP) pesticides. Due to the existence of a luminescence resonance energy transfer (LRET) effect between UCNPs and the pesticide probe (abbreviated as HODN), blue emission at 475 nm of UCNPs was quenched. Interestingly, upon the addition of the pesticide mimic diethyl chlorophosphate (DCP) or the OP pesticide dimethoate, UV absorption of HODN at 475 nm gradually vanished, and the LRET effect was suspended. Consequently, the blue UCL of UCNPs can be recovered well within a very short interval. Since the UCL emission at 803 nm was impervious to the interaction between HODN and pesticides, it can act as an internal standard for the accurate detection of pesticides. Additionally, it was demonstrated that HODN could quantitatively detect dimethoate in the range of 0–80 μM. Importantly, this nanosensor is qualified for the detection of pesticides in pure aqueous solution. Compared with enzymatic and electrochemical based detection methods for OP pesticides, this strategy was much more convenient and economical.

SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic

Owing to the central role of apoptosis in many human diseases and the wide-spread application of apoptosis-based therapeutics, molecular imaging of apoptosis in clinical practice is of great interest for clinicians, and holds great promises. Based on the well-defined biochemical changes for apoptosis, a rich assortment of probes and approaches have been developed for molecular imaging of apoptosis with various imaging modalities. Among these imaging techniques, nuclear imaging (including single photon emission computed tomography and positron emission tomography) remains the premier clinical method owing to their high specificity and sensitivity. Therefore, the corresponding radiopharmaceuticals have been a major focus, and some of them like 99mTc-Annexin V, 18F-ML-10, 18F-CP18, and 18F-ICMT-11 are currently under clinical investigations in Phase I/II or Phase II/III clinical trials on a wide scope of diseases. In this review, we summarize these radiopharmaceuticals that have been widely used in clinical trials and elaborate them in terms of radiosynthesis, pharmacokinetics and dosimetry, and their applications in different clinical stages. We also explore the unique features required to qualify a desirable radiopharmaceutical for imaging apoptosis in clinical practice. Particularly, a perspective of the impact of these clinical efforts, namely, apoptosis imaging as predictive and prognostic markers, early-response indicators and surrogate endpoints, is also the highlight of this review.

A smart self-assembled organic nanoprobe for protein-specific detection: design, synthesis, application and mechanism studies

Specific detection or imaging protein has high potential to contribute greatly to medical diagnosis, biological research, and therapeutic applications. The level of human serum albumin (HSA) in blood is related to a variety of diseases and thus serves as an important biomarker for fast clinical diagnosis. Here we report the use of aggregation-induced emission (AIE) based supramolecular assembly to design biomolecular responsive smart organic nanomaterials for detection protein HSA. The designed nanoprobes were aggregates of small molecules and silent in fluorescence, but in the presence of HSA they disassembled and produced a clear turn-on fluorescent signal. Of a small library of nanoprobes constructed for HSA detection, structure-optical signaling and screening studies revealed that nanoprobe 7 is the most efficient one. Mechanism studies showed that nanoprobe 7 was bonded with Site I of HSA through the multiple noncovalent interactions. The resultant restriction of intramolecular rotation of nanoprobe 7 in the hydrophobic cavity of HSA induced fluorescent emission, which was validated by competitive binding assays and molecular docking. More importantly, nanoprobe 7 was successfully applied to recognize and quantify HSA in human serum samples. This study demonstrates nanoprobe 7 is a promising tool for clinical real and fast detection of HSA and thus may find many applications, and the molecular assembly based on AIE also opens a new avenue for designing smart nanomaterials for the sensitive and selective detection for varied analytes.

Fluorescence dye loaded nano-graphene for multimodal imaging guided photothermal therapy

Photoacoustic imaging (PA) has emerged as a novel and noninvasive imaging modality owing to its high spatial resolution and high soft tissue contrast. Herein, we loaded a near-infrared (NIR) fluorescence dye (CySCOOH) onto the surface of PEGylated graphene oxide (GO) via π-π stacking to increase the NIR absorbance of GO. The PA imaging proved that PEGylated GO-CysCOOH (GO-PEG-CysCOOH) significantly enhances the PA signal in the tumor site compared with free GO-PEG. We then utilized the strong optical absorbance of GO-PEG-CySCOOH in the NIR region for in vivo photothermal therapy, achieving efficient tumor ablation after intravenous injection of GO-PEG-CySCOOH and low-power laser irradiation on the tumor. Our results indicate that this graphene-based nanocomposite can be developed as a promising contrast agent for PA imaging and a thermal agent for imaging guided photothermal therapy.

Microtubule-targeting anticancer agents from marine natural substance.

Effective novel therapeutics is urgently needed due to increasing incidence of malignant cancer and drug multi-resistance. Natural products and their derivatives have historically been a source of pharmaceutical leads and therapeutic drugs. Microtubule-targeting compounds are among the most promising candidates in the combat against cancer. In particular, marine natural products (MNPs) have demonstrated exceptional potency and potential as anticancer agents. Drug discovery from MNPs provides a new pathway to develop original anticancer agents. In this review, seven classes of typical MNPs with diverse structures are summarized. Bioactive marine compounds isolated from different organisms including invertebrate animals, algae, fungi and bacteria are also discussed.

Gene detection: An essential process to precision medicine

Gene detection plays an important role in public health and consumer finances cause its prominent functions in precision medicine, pathogens detection and species identification. Whats more, the announcement of Precision Medicine Initiative would strengthen its status further in many aspects. Therefore, rapid and simplified gene detection techniques are in urgent demand to meet the practical use. During the last decades, gene detection techniques have advanced considerably by integrating various strategies such as microassay, nanotechnologies and electrochemical methods. Herein, we summerized the recent innovations of gene detection methods based on the signal read-out modalities, and highlight those techniques with the potentials to realize Point-of-care (POC) tests. Additionally, gene detection principle, amplification strategies and their applications are also discussed.

Fluorescent probes and materials for detecting formaldehyde: from laboratory to indoor for environmental and health monitoring

Formaldehyde (FA), as a vital industrial chemical, is widely used in building materials and numerous living products. It has become one of the most important air pollutants in residential and industrial occupational environments. Studies have shown that FA easily reacts with nucleophilic materials, leading to the formation of DNA damage. Additionally, Alzheimers disease is related to the intake of FA. The concentration of FA in our surroundings especially in the urban environment has attracted increasing attention. Thus, development of a rapid, sensitive and facile method to determine the concentration of FA becomes highly desirable. To date, many types of FA sensing methods have been applied to detect and quantify FA concentration. Herein, we summarized the recent development of materials for FA detection and their application in environmental and health monitoring, with a focus on fluorescent probe, nanomaterials, and biomolecules. Moreover, the future trend of related development from lab to indoors was also proposed.