Zhen Cheng

Stanford University | SU · Department of Radiology

The therapeutic efficacy of photothermal therapy (PTT) under mild temperatures (<45 °C) is hindered as cancer cells can activate heat shock proteins (HSPs) to mend fever‐type cellular damage swiftly. The previous attempt fabricated first‐generation nanobombs (nanobomb1G) by self‐assembly of polymeric NIR‐II AIEgens and carbon monoxide (CO) carrier...

Background Neuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-¹⁸F-5-fluoropicolinamide (¹⁸F-P3BZA), w...

Phototheranostics has garnered sustained attention due to its significant potential for revolutionizing conventional cancer treatment strategies. While being one of the most commonly employed strategies for constructing phototheranostic systems by engineering the integration of photosensitizers (PSs) into nanosystems, nano‐PSs face challenges inclu...

Purpose Overexpression of Poly (ADP-ribose) polymerase (PARP) is associated with many diseases such as oncological diseases. Several PARP-targeting radiotracers have been developed to detect tumor in recent years. Two ¹⁸F labelled probes based on Olaparib and Rucaparib molecular scaffolds have been evaluated in clinical trials, but their slow hepat...

For its vital role in maintaining cellular activity and survival, mitochondrion is highly involved in various diseases, and several strategies to target mitochondria have been developed for specific imaging and treatment. Among these approaches, theranostic may realize both diagnosis and therapy with one integrated material, benefiting the simplifi...

Despite multifunctional theranostics hold vast potential in deep tissue bioimaging and tumor therapy, activatable nanomedicine with integration of precise diagnosis and effective treatment is usually achieved at the cost of complicated synthesis chemistries. Here, a facile way to design bioresponsive Ag2S‐Ag Janus probes coated by polyethylene glyc...

Nowadays, second near-infrared window (NIR-II) dyes are almost excited by laser diodes, but none of the white light (400–700 nm) excited NIR-II imaging has been studied because of the lack of suitable optical probes. Herein, a novel blue-shifted NIR-II dye, TPA-TQT, has been selected for use in multi-wavelength white light emitting diode (LED) exci...

The mesenchymal epithelial transition factor (c-Met) is frequently overexpressed in numerous cancers and has served as a validated anticancer target. Inter- and intra-tumor heterogeneity of c-Met, however, challenges the use of anti-MET therapies, highlighting an urgent need to develop an alternative tool for visualizing whole-body c-Met expression...

Medical devices are commonly implanted underneath the skin, but how to real‐time noninvasively monitor their migration, integrity, and biodegradation in human body is still a formidable challenge. Here, the study demonstrates that benzyl violet 4B (BV‐4B), a main component in the FDA‐approved surgical suture, is found to produce fluorescence signal...

Mitochondrial membrane potential (ΔΨm)‐targeting molecular probes play an essential role in diagnosing and treating diseases. Recently, the second near‐infrared window (NIR‐II, 1000–1700 nm) fluorescent imaging has been actively studied as an attractive imaging modality. However, small molecule ΔΨm‐targeting NIR‐II probes are rarely reported, espec...

Recently, photothermal therapy (PTT) has attracted enormous attention because of its low invasiveness, high spatiotemporal selectivity, and good therapeutic effect. Different types of photothermal conversion agents have been developed, particularly the second near‐infrared window (NIR‐II, 1000–1700 nm) organic small molecular dyes which have become...

Reactive oxygen species (ROS) are closely related to innate and adaptive immune responses in tumor immu-notherapy. ROS-mediated therapies show great hope in improving therapeutic efficacy by inducing immunogenic cell death. However, the efficiency is still limited by the poor ROS production rate. Herein, a ROS nanogenerator is designed to boost ant...

The second near‐infrared biological window two (NIR‐II, 1000–1700 nm) imaging has made remarkable achievements in fluorescence imaging of diseases. Here, this work takes advantage of the rich spectral properties of rare‐earth doped nanoparticles (RENPs) and their capability to present multiple emission peaks in different luminescence regions simult...

Fluorescent lateral flow immunoassay (LFA) is one of the most common analytical platforms for point-of-care testing (POCT), which is capable of facile and early screening of biomarkers. Notably, fluorescent probes play a decisive role in analytical performances of LFA. Herein, we report a novel LFA based on the rare earth doped nanoparticles (RENPs...

Near-infrared window II (NIR-II, 1000 – 1700 nm) imaging shows high promise for medical applications. Novel NIR-II dyes are the driving force to realize and broaden the biomedical applications of this newly rising imaging technique. Herein, we designed a novel small molecular NIR-II dye IT-TQT using a new strategy and further loaded the dye into DS...

Tumor microenvironment (TME)-activated theranostics is a promising strategy to effectively identify small lesions, improve antitumor efficacy, and reduce the risk of undesired side effects. Hypoxia, as a common characteristic of TME, can serve as a preferred site for stimulus-dependent activation; however, tumor-hypoxia levels in various developmen...

In microsurgery, it is always difficult to accurately identify the blood supply with ease, such as vascular anastomosis, digit replantation, skin avulsion reconstruction and flap transplantation. Near-infrared window I (NIR-I, 700—900 nm) imaging has many clinical applications, whereas near-infrared window II (NIR-II, 1,000–1700 nm) imaging has eme...

Due to the elusive structure-function relationship, traditional nanocatalysts always yield limited catalytic activity and selectivity, making them practically difficult to replace natural enzymes in wide industrial and biomedical applications. Accordingly, single-atom catalysts (SACs), defined as catalysts containing atomically dispersed active sit...

Long Stokes shift dyes that minimize cross-talk between the excitation source and fluorescent emission to improve the signal-to-background ratio are highly desired for fluorescence imaging. However, simple small molecular dyes with large Stokes shift (more than 120 nanometers) and near-infrared (NIR) emissions have been rarely reported so far. Here...

Phototheranostics, relying on energy conversions of fluorophores upon excitation, integrating diagnostic fluorescence imaging and photo-driven therapy, represents a promising strategy for cancer precision medicine. Compared with the first near-infrared biological window (NIR-I), fluorophores imaged in the second window (NIR-II, 1000–1700 nm) exhibi...

Near-infrared window IIb (NIR-IIb, 1500−1700 nm) fluorescence imaging demonstrates attractive properties including low scattering, low absorption, and deep tissue penetration, and photothermal therapy (PTT) is also a promising modality for cancer treatment. However, until now, there is no report on theranostic systems based on small organic molecul...

Nanozymes with multienzyme‐mimicking activities have shown great potential in cancer therapy due to their ability to modulate the complex tumor microenvironment (TME). Herein, a second near‐infrared (NIR‐II) photothermal‐nanocatalyst by decorating Bi2Te3 nanosheets with ultrasmall Au/Pd bimetallic nanoparticles (Bi2Te3‐Au/Pd) to reverse the immunos...

Purpose: The surgery of glioblastoma (GBM) requires a maximal resection of the tumor when it is safe and feasible. The infiltrating growth property of the GBM makes it a challenge for neurosurgeons to identify the tumor tissue even with the assistance of the surgical microscope. This highlights the urgent requirement for imaging techniques that ca...

It is highly important and challenging to develop donor-acceptor-donor structured small-molecule second near-infrared window (NIR-II) dyes with excellent properties such as water-solubility and chem/photostability. Here, we discovery an electron acceptor, 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) with highest stability in alk...

Integrating multiple functionalities of near-infrared second window fluorescence imaging (NIR-Ⅱ FLI), chemotherapy, and photothermal treatment (PTT) into a single molecule is desirable but still a highly challenging task. Herein, inspired by the results that hyperthermia can enhance the cytotoxicity of some alkylating agents, we designed and synthe...

The activatable imaging technique in the second near‐infrared window (NIR‐II) utilizes the stimulation of cancer‐associated biomarkers for specific imaging to guide precise NIR‐II photothermal therapy. However, most activatable nanoprobes with single‐source stimulation are insufficient in providing comprehensive information regarding the tumor, sev...

In the second near-infrared spectral window (NIR-II; with wavelengths of 1,000–1,700 nm), in vivo fluorescence imaging can take advantage of reduced tissue autofluorescence and lower light absorption and scattering by tissue. Here, we report the development and in vivo application of a NIR-II phosphorescent probe that has lifetimes of hundreds of m...

Real-time monitoring of liver dysfunction represents a significant unmet demand in clinical and preclinical research. The second near-infrared window (NIR-II, 1000–1700 nm) fluorescent imaging is an attractive method for biomedical imaging and may be a promising approach for liver dysfunction monitoring. Herein, we designed and synthesized a small-...

The advances of catalysts now enter an era of atomic-level precise control. Single-atom catalysts (SACs), characterized by outstanding catalytic activity and selectivity, afford attractive opportunities to revolutionize traditional nanomedicine.

Purpose: Estrogen receptors beta (ERβ) is an important ER subtype and plays crucial roles in many physiological and pathological disorders. Herein, we aim to develop a probe, ¹⁸F-PVBO, for in vivo ERβ targeted PET imaging with promising results. Methods: 18F-PVBO was synthesized using a two-step radiolabeling method. The relative binding affinities...

Ferroptosis therapy (FT) is an attractive strategy to selectively damage cancer cells through lipid peroxide (LPO) over-accumulation. However, this therapy suffers from poor therapeutic efficacy due to the limited Fenton reaction efficiency and the evolved intrinsic resistance mechanism in the tumor microenvironment (TME). The exploitation of novel...

Objective: This translational study aims to investigate the clinical benefits of indocyanine green (ICG) based near-infrared window II (NIR-II) fluorescence image-guided surgery (FGS) on high-grade glioma (HGG) patients. Methods: Patients were randomly assigned to receive FGS or traditional white light image-guided surgery (WLS). The detection r...

Liver cancer, of which hepatocellular carcinoma (HCC) is the most common form, is one of the most lethal cancers worldwide. The five-year survival rate for HCC is below 9%, which can be attributed to late diagnosis and limited treatment options at the late stage. Therefore, safe and efficient imaging strategies are urgently needed to facilitate HCC...

Featuring simultaneous multicolor imaging for multiple targets, a synergistic strategy has become promising for fluorescence imaging applications. Visible and first near infrared (NIR-I, 700-900 nm) fluorophores have been explored for multicolor imaging to achieve good multi-target capacity, but they are largely hampered by the narrow imaging bands...

The fluorescence imaging in the second near‐infrared window (NIR‐II, 1000–1700 nm) is a very promising and actively studied technique, whereas optical imaging via NIR‐II phosphorescence has been seldom studied. Here, an aggregation‐induced selective signal activation strategy is reported, which relies on switching of radiative mode of probe from we...

Stem cell therapy holds high promises in regenerative medicine. The major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution, migration, and engraftment, which cannot be easily achieved by current techniques. To address this issue, for the first time, we have developed a molecular cell tracke...

In vivo fluorescence imaging in the near-infrared II window (NIR-II, 1000–1700 nm) has great improvements in imaging quality compared with the visible (400–700 nm) and the NIR-I (700–900 nm) window due to the low autofluorescence and the reduced scattering. To date, a variety of NIR-II fluorophores have been synthesized and applied in vivo imaging a...

A small‐molecular‐based self‐assembling and pH‐responding NIR‐II fluorescent nanoprobe is developed by Zhenhua Hu, Jie Tian, Zhen Cheng, and co‐workers in article number 2006902. This nanoprobe sharply responds to a decrease of pH in the tumor microenvironment. It aggregates from small nanoprobes (80 nm at pH 7.0) into large nanoparticles (>500 nm...

Melanin exists in the most of melanoma lesions. Melanin plays an important role in melanoma progression, metastasis, therapy response, and the overall survival of patients. Therefore, melanin is a critical target for melanoma diagnosis and therapy. Many melanin targeting probes, such as radioisotope-labeled benzamide analogs, have been developed fo...

Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near‐infrared window (NIR‐II, 1000–1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH‐sens...

A Correction to this paper has been published: https://doi.org/10.1007/s11307-021-01598-w

Multi‐modality cancer diagnosis techniques based on the second near‐infrared window fluorescence (NIR‐II FL, 1000–1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achie...

Copper(II) diethyldithiocarbamate complex (CuET), the metabolite of disulfiram complexed with copper, is the component responsible for cancer treatment efficacy of disulfiram. But the hydrophobic property of CuET limits its use in vivo, and an appropriate drug delivery system needs to be developed. Ultrasmall melanin nanoparticle (M-Dot) with excel...

Second near-infrared (NIR-II) window (1000–1700 nm) imaging is a highly promising noninvasive imaging technique for preclinical research due to the reduced scattering, minimal absorption, and negligible autofluorescence, affording high resolution and high signal-to-noise ratio images at deep tissue depths. In this chapter, very recent progress achi...

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterol-emia. Here, we report the generation, structure, and function of a first-in-class, fully hum...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully huma...

In article number 2003851, Wang Jia, Zhen Cheng, and co‐workers for the first time present glutathione‐capped gold nanoclusters that demonstrate highly efficient binding capability to hydroxyapatite. The gold nanoclusters can be used for bone imaging with NIR‐II fluorescence and excreted through the renal system, showing great potential for clinica...

Fluorescence imaging in the second near‐infrared window (NIR‐II, 1000–1700 nm) holds great promise for deep tissue visualization. Development of novel clinical translatable NIR‐II probes is crucial for realizing the medical applications of NIR‐II fluorescence imaging. Herein, the glutathione‐capped gold nanoclusters (AuNCs, specifically Au25(SG)18)...

Melanin is a group of natural pigments found in living organism. It can be used for positron emission tomography (PET) imaging due to its inherent chelating ability to radioactive cupric ion. This study was to prepare ⁶⁴Cu-labeled PEGylated Melanin nanoparticles (⁶⁴Cu-PEG-MNPs), and to further take advantage of the enhanced permeability and retenti...

Spurred by newly developed drug delivery systems (DDSs), side effects of cancer chemotherapy could be reduced by using multifunctional nanoplatforms. However, the facile synthesis of effective DDSs remains a challenge. Here, a six-arginine-tailed anti-epidermal growth factor receptor (EGFR) affibody was employed to easily synthesize the highly reac...

Hepatocellular carcinoma (HCC) is a worldwide malignancy and surgical resection remains the most effective treatment. However, it is still a great challenge to locate small lesions and define the border of diffused HCC even with the help of preoperative imaging examination. Here, we reported rare earth doped nanoparticles NaGdF4: Nd5%@NaGdF4@Lips (...

All tumor imaging modalities have resolution limits below which deeply‐situated small metastatic foci may not be identified. Moreover, incomplete lesion excision will affect the outcomes of the patients. Scintigraphy is adept in locating lesions, and second near‐infrared window (NIR‐II) imaging may allow precise real‐time tumor delineation. To achi...

Coronary artery disease (CAD) causes mortality and morbidity worldwide. We used near-infrared erythrocyte-derived transducers (NETs), a contrast agent, in combination with a photoacoustic imaging system to identify the locations of atherosclerotic lesions and occlusion due to myocardial-infarction (MI). NETs (≈90 nm diameter) were fabricated from h...