Zhantong Wang

Gold Nanoparticle-Based Activatable Probe for Sensing Ultralow Levels of Prostate-Specific Antigen

It is still in high demand to develop extremely sensitive and accurate clinical tools for biomarkers of interest for early diagnosis and monitoring of diseases. In this report, we present a highly sensitive and compatible gold nanoparticle (AuNP)-based fluorescence-activatable probe for sensing ultralow levels of prostate-specific antigen (PSA) in patient serum samples. The limit of detection of the newly developed probe for PSA was pushed down to 0.032 pg/mL, which is more than 2 orders of magnitude lower than that of the conventional fluorescence probe. The ultrahigh sensitivity of this probe was attributed to the high loading efficiency of the dyes on AuNP surfaces and high fluorescence quenching-unquenching abilities of the dye-AuNP pairs. The efficiency and robustness of this probe were investigated in patient serum samples, demonstrating the great potential of this probe in real-world applications.

Biomineralization-Inspired Synthesis of Copper Sulfide-Ferritin Nanocages as Cancer Theranostics.

It is essential to control the size and morphology of nanoparticles strictly in nanomedicine. Protein cages offer significant potential for templated synthesis of inorganic nanoparticles. In this study, we successfully synthesized ultrasmall copper sulfide (CuS) nanoparticles inside the cavity of ferritin (Fn) nanocages by a biomimetic synthesis method. The uniform CuS-Fn nanocages (CuS-Fn NCs) showed strong near-infrared absorbance and high photothermal conversion efficiency. In quantitative ratiometric photoacoustic imaging (PAI), the CuS-Fn NCs exhibited superior photoacoustic tomography improvements for real-time in vivo PAI of entire tumors. With the incorporation of radionuclide (64)Cu, (64)CuS-Fn NCs also served as an excellent PET imaging agent with higher tumor accumulation compared to free copper. Following the guidance of PAI and PET, CuS-Fn NCs were applied in photothermal therapy to achieve superior cancer therapeutic efficiency with good biocompatibility both in vitro and in vivo. The results demonstrate that the bioinspired multifunctional CuS-Fn NCs have potential as clinically translatable cancer theranostics and could provide a noninvasive, highly sensitive, and quantitative in vivo guiding method for cancer photothermal therapies in experimental and clinical settings.

Glucose Oxidase-Catalyzed Growth of Gold Nanoparticles Enables Quantitative Detection of Attomolar Cancer Biomarkers

Ultrasensitive and quantitative detection of cancer biomarkers is an unmet challenge because of their ultralow concentrations in clinical samples. Although gold nanoparticle (AuNP)-based immunoassays offer high sensitivity, they were unable to quantitatively detect targets of interest most likely due to their very narrow linear ranges. This article describes a quantitative colorimetric immunoassay based on glucose oxidase (GOx)-catalyzed growth of 5 nm AuNPs that can detect cancer biomarkers from attomolar to picomolar levels. In addition, the limit of detection (LOD) of prostate-specific antigen (PSA) of this approach (93 aM) exceeds that of commercial enzyme-linked immunosorbent assay (ELISA) (6.3 pM) by more than 4 orders of magnitude. The emergence of red or purple color based on enzyme-catalyzed growth of 5 nm AuNPs in the presence of target antigen is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

Acetylcholinesterase‐Catalyzed Hydrolysis Allows Ultrasensitive Detection of Pathogens with the Naked Eye

Major State Basic Research Development Program of China (973 Program) [2013CB733802, 2014CB744503]; National Science Foundation of China (NSFC) [81101101, 51273165, 81201086, 81201190, 81371596]; Key Project of the Chinese Ministry of Education [212149]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH); NIH-NIBIB/NIST NRC

Multimodal-Imaging-Guided Cancer Phototherapy by Versatile Biomimetic Theranostics with UV and γ-Irradiation Protection.

A versatile biomimetic theranostic agent based on magnetic melanin nanoparticles is developed for positron-emission tomography/magnetic resonance/photoacoustic/photothermal multimodal-imaging-guided cancer photothermal therapy and UV and γ-irradiation protection.

Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity

Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin(®) or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection.

Impact of Semiconducting Perylene Diimide Nanoparticle Size on Lymph Node Mapping and Cancer Imaging

Semiconducting molecules of perylene diimide (PDI) with strong light absorption properties in the near-infrared region and good biocompatibility have received increasing attention in the field of theranostics, especially as photoacoustic (PA) imaging agents. Herein, we report a series of [64Cu]-labeled PDI nanoparticles (NPs) of different sizes (30, 60, 100, and 200 nm) as dual positron emission tomography (PET) and PA imaging probes and photothermal therapy agents. The precise size control of the PDI NPs can be achieved by adjusting the initial concentration of PDI molecules in the self-assembly process, and the photophysical property of different sized PDI NPs was studied in detail. Furthermore, we systematically investigated the size-dependent accumulation of the PDI NPs in the lymphatic system after local administration and in tumors after intravenous injection by PA and PET imaging. The results revealed that 100 nm is the best size for differentiating popliteal and sciatic LNs since the interval is around 60 min for the NPs to migrate from popliteal LNs to sciatic LNs, which is an ideal time window to facilitate surgical sentinel LN biopsy and pathological examination. Furthermore, different migration times of the different-sized PDI NPs will provide more choices for surgeons to map the specific tumor relevant LNs. PDI NP theranostics can also be applied to imaging-guided cancer therapy. The NPs with a size of 60 nm appear to be the best for tumor imaging and photothermal cancer therapy due to the maximum tumor accumulation efficiency. Thus, our study not only presents organic PDI NP theranostics but also introduces different-sized NPs for multiple bioapplications.

Virus-mimetic nanovesicles as a versatile antigen-delivery system

Significance The previously unidentified virus-mimetic nanovesicles (VMVs) described in this manuscript consist of phospholipid derived from mammalian cell plasma membrane, recombinant protein anchored to cell membrane via the route of signal peptide sorting, and surfactants capable of controlling the VMV size and strength, which allows the VMVs to display functional polypeptides or maintain the correct conformation of protein antigen. The protein integrated into VMV by its hydrophobic transmembrane peptide has more modifications, such as glycosylation, than proteins in conventional subunit vaccines. Moreover, many viral envelope glycoproteins can be genetically engineered onto VMV liposomal surface so as to mimic the properties and conformational epitopes of natural virus. VMV provides an effective, straightforward, and tunable approach against a wide range of emerging enveloped viruses. It is a critically important challenge to rapidly design effective vaccines to reduce the morbidity and mortality of unexpected pandemics. Inspired from the way that most enveloped viruses hijack a host cell membrane and subsequently release by a budding process that requires cell membrane scission, we genetically engineered viral antigen to harbor into cell membrane, then form uniform spherical virus-mimetic nanovesicles (VMVs) that resemble natural virus in size, shape, and specific immunogenicity with the help of surfactants. Incubation of major cell membrane vesicles with surfactants generates a large amount of nano-sized uniform VMVs displaying the native conformational epitopes. With the diverse display of epitopes and viral envelope glycoproteins that can be functionally anchored onto VMVs, we demonstrate VMVs to be straightforward, robust and tunable nanobiotechnology platforms for fabricating antigen delivery systems against a wide range of enveloped viruses.

Magneto‐Plasmonic Janus Vesicles for Magnetic Field‐Enhanced Photoacoustic and Magnetic Resonance Imaging of Tumors

Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation (T2 ) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2-3 times in the PA and MR imaging, compared with control groups without a magnetic field.

Core–Satellite Polydopamine–Gadolinium-Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.