GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling.

The high mortality rate associated with gastric cancer (GC) has resulted in an urgent need to identify novel therapeutic targets for GC. This study aimed to investigate whether GAIP interacting protein, C terminus 1 (GIPC1) represents a therapeutic target and its regulating mechanism in GC. GIPC1 expression was elevated in GC tissues, liver metastasis tissues, and lymph node metastases.

Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis.

The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation.

Monoclonal Antibody-Guided Tumor-Targeted Hollow Virus-Like Cerium Oxide with Oxygen Self-Supply for Intensifying Photodynamic Therapy.

The hypoxic character of tumors and the poor targeting ability of photosensitizers often limit the efficacy of photodynamic therapy (PDT). In recent years, the discovery of metal nanoenzymes and nanocarriers has improved PDT. Thereby, to improve the effective utilization of photosensitizers and oxygen (O ) in tumors, herein, a nanosystem (LS-HB@HvCeO -NRP1 mAb, LHCN1) is reported, in which a hollow virus-like cerium oxide (HvCeO ) is surface-decorated with tumor-targeting neuropilin-1 monoclonal antibody (NRP1 mAb), and loaded with a photosensitizer (chlorin e6-C-15-ethyl ester, LS-HB).

AKR1B10 accelerates the production of proinflammatory cytokines via the NF-κB signaling pathway in colon cancer.

Aldo-keto reductase family one, member B10 (AKR1B10) has been reported to be involved in the tumorigenesis of various cancers. It has been reported that colorectal cancer is closely associated with chronic inflammation, but the underlying molecular mechanisms are still elusive. In our study, we evaluated the relationship between AKR1B10 expression and clinicopathological characteristics of colon cancer and showed that AKR1B10 expression was significantly correlated with the T stage and clinical stage of colon cancer.

Self-Delivering Nanodrugs Developed via Small-Molecule-Directed Assembly and Macrophage Cloaking for Sonodynamic-Augmented Immunotherapy.

The self-delivery of sonosensitizers and immunomodulators to tumor areas, which is highly recommended for enhancing sonodynamic immunotherapy, remains a challenge. Herein, a self-delivering nanodrug (HB-NLG8189, drug loading: ≈100 wt%) is developed by the small-molecule self-assembly of "HB" (a new clinical photosensitizer) and NLG8189 (indoleamine-(2,3)-dioxygenase (IDO) pathway inhibitor) for sonodynamic-augmented immunotherapy; this preparation method ensures the absence of excipient-related toxicity and immunogenicity. To evade immune recognition and prolong the circulation time, the HB-NLG8189 nanodrugs are camouflaged using macrophage cell membranes (MPCMs).

LS-HB-Mediated Photodynamic Therapy Inhibits Proliferation and Induces Cell Apoptosis in Melanoma.

Chlorin e6-C-15-ethyl ester (LS-HB), a newly identified photosensitizer, was isolated from chlorin e6. The mechanism of tumor cell death induced by photodynamic therapy with LS-HB (LS-HB-PDT) is still unknown. Here, we investigated the photophysical properties of LS-HB, evaluated the antitumor effect on melanoma and , and explored its possible mechanisms.

pH-Responsive Liposomes Loaded with Targeting Procoagulant Proteins as Potential Embolic Agents for Solid Tumor-Targeted Therapy.

Selectively inducing tumor thrombosis and subsequent necrosis is a novel and promising antitumor strategy. We have previously designed a targeting procoagulant protein, called tTF-EG3287, which is a fusion of a truncated tissue factor (tTF) with EG3287, a short peptide against the neuropilin-1 (NRP1) binding site of vascular endothelial growth factor-A 165 (VEGF-A 165). However, off-target effects and high-dose requirements limit the further use of tTF-EG3287 in antitumor therapy.

Virus-Inspired Hollow Mesoporous Gadolinium-Bismuth Nanotheranostics for Magnetic Resonance Imaging-Guided Synergistic Photodynamic-Radiotherapy.

The anti-tumor efficacy of single photodynamic therapy (PDT) and radiotherapy (RT) has been greatly affected by inadequate tumor uptake of photo/radiation sensitizers, limited laser penetration depth, and radiation sickness caused by high doses of X-rays. Here, the authors report a biomimetic coronavirus-inspired hollow mesoporous gadolinium/bismuth nanocarrier loaded with a new NIR photosensitizer HB (termed as HB@VHMBi-Gd) for magnetic resonance imaging (MRI)-guided synergistic photodynamic-RT. HB@VHMBi-Gd displayed a faster cellular uptake rate than the conventional spherical HMBi-Gd loaded with HB (HB@SHMBi-Gd) because of rough surface-enhanced adhesion.

Virus-Inspired Gold Nanorod-Mesoporous Silica Core-Shell Nanoparticles Integrated with tTF-EG3287 for Synergetic Tumor Photothermal Therapy and Selective Therapy for Vascular Thrombosis.

Synergetic therapy includes the combination of two or more conventional therapeutic approaches and can be used for tumor treatment by combining the advantages and avoiding the drawbacks of each type of treatment. In the present study, truncated tissue factor (tTF)-EG3287 fusion protein-encapsulated gold nanorod (GNR)-virus-inspired mesoporous silica core-shell nanoparticles (vinyl hybrid silica nanoparticles; VSNP) (GNR@VSNP-tTF-EG3287) were synthesized to achieve synergetic therapy by utilizing selective vascular thrombosis therapy (SVTT) and photothermal therapy (PTT). By integrating the targeted coagulation activity of tTF-EG3287 and the high tumor ablation effect of GNR@VSNP, local hyperthermia could induce a high percentage of apoptosis of vascular endothelial cells by using near-infrared light.

New-generation photosensitizer-anchored gold nanorods for a single near-infrared light-triggered targeted photodynamic-photothermal therapy.

Traditional combined photodynamic and photothermal therapy (PDT/PTT) was limited in clinical treatment of cancer due to the exceptionally low drug delivery efficiency to tumor sites and the activation by laser excitation with different wavelengths. We have accidentally discovered that our synthesized chlorin e6-C-15-ethyl ester (HB, a new type of photosensitizer) be activated by a laser with an excitation wavelength of 660 nm. Herein, we utilized Au nanorods (AuNRs) as 660 nm-activated PTT carriers to be successively surface-functionalized with HB and tumor-targeting peptide cyclic RGD (cRGD) to develop HB-AuNRs@cRGD for single NIR laser-induced targeted PDT/PTT.

An outstanding role of novel virus-like heterojunction nanosphere BOCO@Ag as high performance antibacterial activity agent.

The development of highly efficient photonic nanomaterials with synergistic biological effects is critical and challenging task for public hygiene health well-being and has attracted extensive interest. In this study, a type of near-infrared (NIR) driven, virus-like heterojunction was first developed for synergistic biological application. The Ag-coated BiCO nanomaterial (BOCO@Ag) demonstrated good biocompatibility, low cytotoxicity, high antibacterial activity and excellent light utilization stability.

Facile Fabrication of BiF: Ln (Ln = Gd, Yb, Er)@PVP Nanoparticles for High-Efficiency Computed Tomography Imaging.

X-ray computed tomography (CT) has been widely used in clinical practice, and contrast agents such as Iohexol are often used to enhance the contrast of CT imaging between normal and diseased tissue. However, such contrast agents can have some toxicity. Thus, new CT contrast agents are urgently needed.

N2E4, a Monoclonal Antibody Targeting Neuropilin-2, Inhibits Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma Suppressing FAK/Erk/HIF-1α Signaling.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with extremely limited treatment; the effective targeting strategy stays an urgent unmet need. Neuropilin-2 (NRP2), a multifunctional transmembrane non-tyrosine-kinase glycoprotein, enhances various signal transduction pathways to modulate cancer progression. However, the application value of NRP2 as a therapeutic target in pancreatic cancer is still unclear.

Construction of Smart Nanotheranostic Platform Bi-Ag@PVP: Multimodal CT/PA Imaging-Guided PDT/PTT for Cancer Therapy.

High-efficiency nanotheranostic agents with multimodal imaging guidance have attracted considerable interest in the field of cancer therapy. Herein, novel silver-decorated bismuth-based heterostructured polyvinyl pyrrolidone nanoparticles (NPs) with good biocompatibility (Bi-Ag@PVP NPs) were synthesized for accurate theranostic treatment, which can integrate computed tomography (CT)/photoacoustic (PA) imaging and photodynamic therapy/photothermal therapy (PDT/PTT) into one platform. The Bi-Ag@PVP NPs can enhance light absorption and achieve a better photothermal effect than bismuth NPs.

AKR1B10 negatively regulates autophagy through reducing GAPDH upon glucose starvation in colon cancer.

Autophagy is considered to be an important switch for facilitating normal to malignant cell transformation during colorectal cancer development. Consistent with other reports, we found that the membrane receptor Neuropilin1 (NRP1) is greatly upregulated in colon cancer cells that underwent autophagy upon glucose deprivation. However, the mechanism underlying NRP1 regulation of autophagy is unknown.

Hetero-Core-Shell BiNS-Fe@Fe as a Potential Theranostic Nanoplatform for Multimodal Imaging-Guided Simultaneous Photothermal-Photodynamic and Chemodynamic Treatment.

Photothermal/photodynamic therapy (PTT/PDT) and synergistic therapeutic strategies are often sought after, owing to their low side effects and minimal invasiveness compared to chemotherapy and surgical treatments. However, in spite of the development of the most PTT/PDT materials with good tumor-inhibitory effect, there are some disadvantages of photosensitizers and photothermal agents, such as low stability and low photonic efficiency, which greatly limit their further application. Therefore, in this study, a novel bismuth-based hetero-core-shell semiconductor nanomaterial BiNS-Fe@Fe with good photonic stability and synergistic theranostic functions was designed.

Anticancer effect of LS-HB-mediated photodynamic therapy on hepatocellular carcinoma in vitro and in vivo.

Unlabelled: Photodynamic therapy (PDT) is a relatively safe way for disease diagnosis and treatment that is based on light and photosensitizers. LS-HB is a promising photosensitizer with a light absorption peak of 660 nm.

Aims: The present study aimed to investigate the anticancer effects of LS-HB-PDT on hepatocellular carcinoma and its underlying molecular mechanism.

Design and construction of a magnetic targeting pro-coagulant protein for embolic therapy of solid tumors.

In this study, we have designed a magnetic targeting pro-coagulant protein (MTPCP) for the embolic therapy of solid tumours. The MTPCP consists of a magnetic carrier and a pro-coagulant protein. The pro-coagulant protein used in this study is the fusion protein tTF-EG3287 which is not pro-coagulant when free in the blood circulation, but presents strong pro-coagulant ability once bound to the Neuropilin-1(NRP-1) that is highly expressed on tumour-associated vascular endothelial cells.

Optimal Saturated Neuropilin-1 Expression in Normal Tissue Maximizes Tumor Exposure to Anti-Neuropilin-1 Monoclonal Antibody.

Background: As involved in tumor angiogenesis, Neuropilin Receptor type-1 (NRP-1) serves as an attractive target for cancer molecular imaging and therapy. Widespread expression of NRP-1 in normal tissues may affect anti-NRP-1 antibody tumor uptake.

Objective: To assess a novel anti-NRP-1 monoclonal antibody A6-11-26 biodistribution in NRP-1 positive tumor xenograft models to understand the relationships between dose, normal tissue uptake and tumor uptake.

Pharmacokinetics and Tissue Distribution of DVDMS-2 in Tumor-bearing Mice.

DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay.

pH-responsive stearic acid-O-carboxymethyl chitosan assemblies as carriers delivering small molecular drug for chemotherapy.

Recently, chemotherapy is still widely exploited to treat the residual, infiltrative tumor cells after surgical resection. However, many anticancer drugs are limited in clinical application due to their poor water-solubility (hydrophibic) and stability, low bioavailability, and unfavorable pharmacokinetics. Herein, an amphiphilic stearic acid-O-carboxymethyl chitosan (SA-CMC) conjugate was synthesized by amide linkage of SA to the backbone of CMC polymer and then self-assembled into nanoparticles (SA-CMC NPs) with the hydrodynamic particle size of ~100 nm.

Construction and characterization of a truncated tissue factor‑coagulation‑based composite system for selective thrombosis in tumor blood vessels.

The selective induction of tumor vascular thrombosis using truncated tissue factor (tTF) delivered via a target ligand is a promising novel antitumor strategy. In the present study, an anti‑neuropilin‑1 (NRP‑1) monoclonal antibody (mAb)‑streptavidin (SA):tTF‑biotin (B) composite system was established. In this system, anti‑NRP‑1‑mAb located tTF to the tumor vascular endothelial cell surface and induced vascular embolization.

Tp47 induces cell death involving autophagy and mTOR in human microglial HMO6 cells.

Background: Tp47 can induce immune cells to produce numerous inflammatory factors, some of which can trigger autophagy. Increased autophagy has a dual effect on cell survival. However, whether Tp47 induces autophagy in microglia is unknown.

Metabolite Profiles of the Cerebrospinal Fluid in Neurosyphilis Patients Determined by Untargeted Metabolomics Analysis.

The mechanism underlying the stealth property of neurosyphilis is still unclear. Global metabolomics analysis can provide substantial information on energy metabolism, physiology and possible diagnostic biomarkers and intervention strategies for pathogens. To gain better understanding of the metabolic mechanism of neurosyphilis, we conducted an untargeted metabolomics analysis of cerebrospinal fluid (CSF) from 18 neurosyphilis patients and an identical number of syphilis/non-neurosyphilis patients and syphilis-free patients using the Agilent, 1290 Infinity LC system.