Xuening Zhang

Size-Tuning Ionization To Optimize Gold Nanoparticles for Simultaneous Enhanced CT Imaging and Radiotherapy

Computed tomography (CT) contrast and radiosensitization usually increase with particle sizes of gold nanoparticles (AuNPs), but there is a huge challenge to improve both by adjusting sizes under the requirements of in vivo application. Here, we report that AuNPs have great size-dependent enhancements on CT imaging as well as radiotherapy (RT) in the size range of 3-50 nm. It is demonstrated that AuNPs with a size of ∼13 nm could simultaneously possess superior CT contrast ability and significant radioactive disruption. The Monte Carlo method is further used to evaluate this phenomenon and indicates that the inhomogeneity of gold atom distributions caused by sizes may influence secondary ionization in whole X-ray interactions. In vivo studies further indicate that this optimally sized AuNP improves real-time CT imaging and radiotherapeutic inhibition of tumors in living mice by effective accumulation at tumors with prolonged in vivo circulation times compared to clinically used small-molecule agents. These results suggest that ∼13 nm AuNPs may serve as multifunctional adjuvants for clinical X-ray theranostic application.

A UCN@mSiO2@cross-linked lipid with high steric stability as a NIR remote controlled-release nanocarrier for photodynamic therapy

In clinics, the application of photodynamic therapy (PDT) in deep tissue is severely constrained by the limited penetration depth of visible light that was used for activating the photosensitizer (PS). In this work, a protocol of a UCN@SiO2@crosslinked lipid triple layer nanoparticle was developed successfully. The triple layer nanoparticle was assembled from the hydrophobic upconverting nanoparticle (UCN) core, the mesoporous silica middle shell and the cross-linked lipid out shell. The photosensitizer zinc phthalocyanine (ZnPc) loaded triple layer nanoparticle offers possibilities to solve the problem mentioned above. The UCN core works as a transducer to convert deeply penetrating near infrared light to visible light for activating ZnPc for photo dynamic therapy. The middle shell is used for loading ZnPc and the out shell can prevent the drug leaking effectively. The experiment results showed that with the help of the cross-linked lipid shell, the triple layer nanoparticle could prevent the drug leaking and particle aggregation. The ROS production test and PDT test suggested that the fluorescence emitted from the UCNs excited by NIR can effectively activate the photosensitizer ZnPc to generate cytotoxic ROS. The UCN@SiO2@crosslinked lipid triple layer nanoparticle modified with RGD has a much better treatment effect in cancer cells. Our data suggest that the UCN@SiO2@crosslinked lipid triple layer nanoparticle may be a useful nanoplatform for future PDT treatment in deep cancer therapy based on the upconverting mechanism.

PB@Au Core-Satellite Multifunctional Nanotheranostics for Magnetic Resonance and Computed Tomography Imaging in Vivo and Synergetic Photothermal and Radiosensitive Therapy

To integrate multiple diagnostic and therapeutic strategies on a single particle through simple and effective methods is still challenging for nanotheranostics. Herein, we develop multifunctional nanotheranostic PB@Au core-satellite nanoparticles (CSNPs) based on Prussian blue nanoparticles (PBNPs) and gold nanoparticles (AuNPs), which are two kinds of intrinsic theranostic nanomaterials, for magnetic resonance (MR)-computed tomography (CT) imaging and synergistic photothermal and radiosensitive therapy (PTT-RT). PBNPs as cores enable T1- and T2-weighted MR contrast and strong photothermal effect, while AuNPs as satellites offer CT enhancement and radiosensitization. As revealed by both MR and CT imaging, CSNPs realized efficient tumor localization by passively targeted accumulation after intravenous injection. In vivo studies showed that CSNPs resulted in synergistic PTT-RT action to achieve almost entirely suppression of tumor growth without observable recurrence. Moreover, no obvious systemic toxicity of mice confirmed good biocompatibility of CSNPs. These results raise new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.

Multimodality imaging in nanomedicine and nanotheranostics

Accurate diagnosis of tumors needs much detailed information. However, available single imaging modality cannot provide complete or comprehensive data. Nanomedicine is the application of nanotechnology to medicine, and multimodality imaging based on nanoparticles has been receiving extensive attention. This new hybrid imaging technology could provide complementary information from different imaging modalities using only a single injection of contrast agent. In this review, we introduce recent developments in multifunctional nanoparticles and their biomedical applications to multimodal imaging and theragnosis as nanomedicine. Most of the reviewed studies are based on the intrinsic properties of nanoparticles and their application in clinical imaging technology. The imaging techniques include positron emission tomography, single-photon emission computed tomography, computerized tomography, magnetic resonance imaging, optical imaging, and ultrasound imaging.

Functional nanocarrier for drug and gene delivery via local administration in mucosal tissues

Local administration has many advantages for treating diseases. However, the surface mucus layer becomes a major obstacle that easily traps and fast removes local administrated drugs and genes in mucosal tissues. Fortunately, the rapidly developing nanocarriers with special physical and chemical properties may help to refine the treatment of mucosal tissues via delivering drugs and genes to the target tissue, and prolong the drug action time. Therefore, this review focuses on the strategies to apply different nanocarriers for drug-delivery in mucosal tissues, including mucoadhesive and mucus-penetrating types. Delivering drugs and genes to anatomical sites with high mucus turnover becomes more feasible and effective, and maintains sufficient local drug concentration to improve treatment efficacy.

Micro- and nano-carrier systems: The non-invasive and painless local administration strategies for disease therapy in mucosal tissues

Mucus is a viscoelastic and adhesive obstacle which protects vaginas, eyes and other mucosal surfaces against foreign pathogens. Numerous diseases that affect the mucosa could be afforded prophylactic and therapeutic treatments with fewer systemic side effects if drugs and genes could be sufficiently delivered to the target mucosal tissues. But drugs and genes are trapped effectively like other pathogens and rapidly removed by mucus clearance mechanism. The emergence of micro- and nano-delivery technologies combined with the realization of non-invasive and painless administration routes brings new hope for the treatment of disease. For retained drugs and genes to mucosal tissues, carriers must increase retention time in the mucus to make full contact with epithelial cells and be transported to target tissues. This review focuses on the current development of micro- and nano-carriers to improve the localized therapeutic efficiency of targeted and sustained drug and gene delivery in mucosal tissues.

Ultrasmall bimodal Nanomolecules enhanced tumor angiogenesis contrast with endothelial cell targeting and molecular pharmacokinetics

Nonintrusive and precise imaging for tumor angiogenesis is critical in accurate assessment of cancer diagnosis and prognosis. However, reticulo-endothelial system (RES) capture and inadequate accumulation remain major bottlenecks for current nanoparticle to retain at tumor angiogenesis site. Herein, we report the ultrasmall contrast agent (cNGR-Au:Gd@GSH NMs) could accumulate at tumor vasculature site and enhance the tumor angiogenesis-contrast. It is demonstrated that by loading Au and Gd atom into the naturally-occurring glutathione (GSH) shell with cNGR peptide modification, cNGR-Au:Gd@GSH NMs exhibit the high X-ray photon absorption, longer rotational correlation time and efficient tumor vascular endothelia cell targeting. In vivo studies further indicate the cNGR-Au:Gd@GSH NMs prominently enhance tumor angiogenesis-contrast both on the computed tomography (CT) and magnetic resonance imaging (MRI) modalities by escaping the RES capture and target delivering. Our data imply that the cNGR-Au:Gd@GSH NMs may serve as the high-efficiency contrast agent to assess tumor angiogenesis in a nonintrusive technique.

Contrast-enhanced US for characterization of focal liver lesions: a comprehensive meta-analysis

AbstractObjectivesThis meta-analysis was performed to evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in differentiating malignant from benign focal liver lesions (FLLs).MethodsCochrane Library, PubMed and Web of Science databases were systematically searched and checked for studies using CEUS in characterization of FLLs. Data necessary to construct 2×2 contingency tables were extracted from included studies. The QUADAS tool was utilized to assess the methodologic quality of the studies. Meta-analysis included data pooling, subgroup analyses, meta-regression and investigation of publication bias was comprehensively performed.ResultsFifty-seven studies were included in this meta-analysis and the overall diagnostic accuracy in characterization of FLLs was as follows: pooled sensitivity, 0.92 (95%CI: 0.91–0.93); pooled specificity, 0.87 (95%CI: 0.86–0.88); diagnostic odds ratio, 104.20 (95%CI: 70.42–154.16). Subgroup analysis indicated higher diagnostic accuracy of the second-generation contrast agents (CAs) than the first-generation CA (Levovist; DOR: 118.27 vs. 62.78). Furthermore, Sonazoid demonstrated the highest diagnostic accuracy among three major CAs (SonoVue, Levovist and Sonazoid; DOR: 118.82 vs. 62.78 vs. 227.39). No potential publication bias was observed of the included studies.ConclusionCEUS is an accurate tool to stratify the risk of malignancy in FLLs. The second-generation CAs, especially Sonazoid may greatly improve diagnostic performance.Key Points• CEUS shows excellent diagnostic accuracy in differentiating malignant from benign FLLs. • The second-generation CAs have higher diagnostic accuracy than first-generation CAs. • Sonazoid demonstrates the highest diagnostic accuracy among three major CAs.