Pancreatic ductal adenocarcinoma, as one of the most aggressive cancers, is characterized by rich desmoplastic stroma that forms a physical barrier for anticancer drugs. To address this issue, we ...herein report a two-step sequential delivery strategy for targeted therapy of pancreatic cancer with gemcitabine (GEM). In this sequential strategy, metformin (MET) was first administrated to disrupt the dense stroma, based on the fact that MET downregulated the expression of fibrogenic cytokine TGF-β to suppress the activity of pancreatic stellate cells (PSCs), through the 5′-adenosine monophosphate-activated protein kinase pathway of PANC-1 pancreatic cancer cells. In consequence, the PSC-mediated desmoplastic reactions generating α-smooth muscle actin and collagen were inhibited, which promoted the delivery of GEM and pH (low) insertion peptide (pHLIP) comodified magnetic nanoparticles (denoted as GEM-MNP-pHLIP). In addition, pHLIP largely increased the binding affinity of the nanodrug to PANC-1 cells. The targeted delivery and effective accumulation of MET/GEM-MNP-pHLIP in vivo were confirmed by magnetic resonance imaging enhanced by the underlying magnetic nanoparticles. The tumor growth inhibition of the sequential MET and GEM-MNP-pHLIP treatment were investigated on both subcutaneous and orthotopic tumor mice models. A remarkably improved therapeutic efficacy, for example, up to 91.2% growth inhibition ratio over 30 d of treatment, well-exemplified the novel cascade treatment for pancreatic cancer and the innovative use of MET.
Abstract
Magnetic resonance (MR) angiography is one of the main diagnostic approaches for cardiac-cerebral vascular diseases. Nevertheless, the non-contrast-enhanced MR angiography suffers from its ...intrinsic problems derived from the blood flow-dependency, while the clinical Gd-chelating contrast agents are limited by their rapid vascular extravasation. Herein, we report a hypersensitive MR angiography strategy based on interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd). The longitudinal molar relaxivity of PAA-Gd was 4.6-times higher than that of individual Gd-chelates as well as appropriate blood half-life (73.8 min) and low immunogenicity, enabling sophisticated micro-vessels angiography with a resolution at the order of hundred micrometers. A series of animal models of cardiac-cerebrovascular diseases have been built for imaging studies on a 7.0 T MRI scanner, while the clinical translation potential of PAA-Gd has been evaluated on swine on a 3.0 T clinical MRI scanner. The current studies offer a promising strategy for precise diagnosis of vascular diseases.
A vast majority of cancer deaths occur as a result of metastasis. Unfortunately, effective treatments for metastases are currently lacking due to the difficulty of selectively targeting these small, ...delocalized tumors distributed across a variety of organs. However, nanotechnology holds tremendous promise for improving immunotherapeutic outcomes in patients with metastatic cancer. In contrast to conventional cancer immunotherapies, rationally designed nanomaterials can trigger specific tumoricidal effects, thereby improving immune cell access to major sites of metastasis such as bone, lungs, and lymph nodes, optimizing antigen presentation, and inducing a persistent immune response. This paper reviews the cutting-edge trends in nano-immunoengineering for metastatic cancers with an emphasis on different nano-immunotherapeutic strategies. Specifically, it discusses directly reversing the immunological status of the primary tumor, harnessing the potential of peripheral immune cells, preventing the formation of a pre-metastatic niche, and inhibiting the tumor recurrence through postoperative immunotherapy. Finally, we describe the challenges facing the integration of nanoscale immunomodulators and provide a forward-looking perspective on the innovative nanotechnology-based tools that may ultimately prove effective at eradicating metastatic diseases.
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•The state of the art for nanotechnology-enabled cancer immunotherapy and the emerging concepts in nano-based immunomodulation are summarized•The cutting-edge trends in nano-immunoengineering for metastatic cancers with an emphasis on different nano-immunotherapeutic strategies are highlighted•Benefits, challenges, and opportunities of nanoscale immunomodulators and a forward-looking perspective on the innovative nanotechnology-based tools that may ultimately prove effective at eradicating metastatic diseases are presented
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•A low-immunogenic magnetic resonance imaging (MRI) nanoprobe with prolonged blood half-life is designed.•The nanoprobe can itinerate in bloodstream to depict the spatial distribution ...of collateral vessels in vivo after stroke.•Through nanoprobe-based MRI, the infarct core, collateral vessels, and ischemic penumbra can be identified simultaneously.
Ischemic stroke is one of the leading causes of disability and mortality. The collaterals provide an alternative pathway to preserve the ischemic brain tissue, and determine the penumbra range, where the neurons are salvageable. Therefore, accurately monitoring the collaterals and identifying the penumbra are crucial. Herein, a low-immunogenic nanoprobe-based MRI strategy is developed to simultaneously identify the infarct core, collaterals distribution, and ischemic penumbra distributions. The low-immunogenic nanoprobe was constructed by covalently attaching self-peptide on the surface of biocompatible Fe3O4 nanoparticles as a stealth coating. Both in vitro and in vivo experiments clearly revealed that the nanoprobes can effectively avoid capture by macrophages, and exhibited prolonged blood half-life to continuously enhance the contrast of blood vessels in a longer time window in susceptibility-weighted imaging (SWI), which enabled the delineation of the collaterals and ischemic penumbra. More importantly, combined with the diffusion-weighted imaging (DWI), the infarct core, collateral vessels, and the ischemic penumbra range can be identified simultaneously. In this context, the stroke progress including infarct core growth, collateral vessel formation, and penumbra distribution, can be better understood. This nanoprobe-based strategy thus offers a practical route for precise diagnosis of ischemic stroke, which remains a challenge for conventional MRI strategies.
The capsule endoscopy robot can only use monocular vision due to the dimensional limit. To improve the depth perception of the monocular capsule endoscopy robot, this paper proposes a photometric ...stereo-based depth map reconstruction method. First, based on the characteristics of the capsule endoscopy robot system, a photometric stereo framework is established. Then, by combining the specular property and Lambertian property of the object surface, the depth of the specular highlight point is estimated, and the depth map of the whole object surface is reconstructed by a forward upwind scheme. To evaluate the precision of the depth estimation of the specular highlight region and the depth map reconstruction of the object surface, simulations and experiments are implemented with synthetic images and pig colon tissue, respectively. The results of the simulations and experiments show that the proposed method provides good precision for depth map reconstruction in monocular capsule endoscopy.
Malignant tumors have been one of the major reasons for deaths worldwide. Timely and accurate diagnosis as well as effective intervention of tumors play an essential role in the survival of patients. ...Genomic instability is the important foundation and feature of cancer, hence, in vivo oncogene imaging based on novel probes provides a valuable tool for the diagnosis of cancer at early-stage. However, the in vivo oncogene imaging is confronted with great challenge, due to the extremely low copies of oncogene in tumor cells. By combining with various novel activatable probes, the molecular imaging technologies provide a feasible approach to visualize oncogene in situ, and realize accurate treatment of tumor. This review aims to declare the design of nanoprobes responded to tumor associated DNA or RNA, and summarize their applications in detection and bioimaging for tumors. The significant challenges and prospective of oncogene-targeting nanoprobes towards tumors diagnosis are revealed as well.
Background
Approximately 30% of patients with oestrogen receptor (ER)-positive breast cancer (BC) exhibit intrinsic or recurrent resistance to tamoxifen (TAM) adjuvant endocrine therapy. The androgen ...receptor (AR) is expressed in about 90% of ER-positive patients. Our previous studies found that BC patients with an AR:ER expression ratio ≥ 2.0 are more susceptible to TAM resistance. However, the specific mechanism by which a high AR:ER ratio promotes TAM resistance remains unknown.
Methods
RNA sequencing was performed on 10 cases of BC tissues with AR:ER ratios ≥ 2.0 and 3 cases with AR:ER ratios < 2.0. We then compared our data with the screened TAM-resistant and TAM-sensitive cases from the TCGA BC database. Bioinformatics methods were used to screen differentially expressed genes (DEGs) and to perform gene enrichment analysis. Weighted correlation network analysis (WGCNA) was used to screen hub genes in the AR-induced TAM resistance process.
Results
PAM50 analysis showed that the molecular phenotype of BC patients with
AR:ER ratios ≥ 2.0 was similar to that of triple-negative breast cancer (TNBC), whereas the BC samples with AR:ER ratios < 2.0 were classified as the luminal subtype. Among the AR:ER ratio ≥ 2.0 and AR:ER < 2.0 BC tumours, 1855 DEGs were identified. Gene enrichment analysis showed that DEGs were enriched mainly in proliferation-related molecular pathways, such as the cell cycle, necroptosis, metabolic pathways and DNA replication. WGCNA analysis showed that SEC14L2, RIIAD1, STC2 and MAGEA6 served as hub genes in AR-induced TAM resistance and were associated with BC survival prognosis in the TCGA cohort.
Conclusions
A high AR:ER expression ratio is a biomarker for patients who might develop TAM resistance, and AR expression seems to be a possible mechanism of resistance to endocrine therapy.
Determining therapeutic efficacy is critical for tumor precision theranostics. In order to monitor the efficacy of anti-cancer drugs (e.g., Paclitaxel), a pH-sensitive ratiometric fluorescent imaging ...probe was constructed. The pH-sensitive ratiometric fluorescent dye ANNA was covalently coupled to the N-terminal of the cell-penetrating TAT peptide through an amidation reaction (TAT-ANNA). The in vitro cellular experiments determined that the TAT-ANNA probe could penetrate the cell membrane and image the intracellular pH in real time. The in vivo experiments were then carried out, and the ratiometric pH response to the state of the tumor was recorded immediately after medication. The TAT-ANNA probe was successfully used to monitor the pharmacodynamics of anti-cancer drugs in vivo.
Aiming to determine the inaccurate image segmentation of strawberries with varying maturity levels due to fruit adhesion and stacking, this study proposed a strawberry image segmentation method based ...on the improved DeepLabV3+ model. The technique introduced the attention mechanism into the backbone network and the atrous spatial pyramid pooling module of the DeepLabV3+ network, adjusted the weights of feature channels in the neural network propagation process through the attention mechanism to enhance the feature information of strawberry images, reduced the interference of environmental factors, and improved the accuracy of strawberry image segmentation. The experimental results showed that the proposed method can accurately segment images of strawberries with different maturities; the mean pixel accuracy and mean intersection over union of the model were 90.9% and 83.05%, respectively, and the frames per second (FPS) was 7.67. The method can effectively reduce the influence of environmental factors on strawberry image segmentation and provide an effective approach for accurate operation of strawberry picking robots.
Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of ...bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with important challenges, including drug resistance, low bioavailability, and adverse side effects; the existence of physiological barriers further hampers treatment. Fortunately, these limitations may be overcome by the application of nanotechnology, which can facilitate drug delivery while improving drug stability and bioavailability. This review summarizes the challenges facing the treatment of bacterial pneumonia and also highlights the types of nanoparticles that can be used for antibiotic delivery. This review places a special focus on the state-of-the-art in nanomaterial-based approaches to the delivery of antibiotics for the treatment of pneumonia.
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