Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-α5β1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.

Chemokine ligand 13 (CXCL13) is believed to play a role in the recruitment of B cells in the central nervous system during neuroinflammation. Neurosyphilis is a group of clinical syndromes of the central nervous system caused by Treponema pallidum (T. pallidum) infection. The relationship between CXCL13 and neurosyphilis still needs further study. In our study, CSF and serum CXCL13 concentrations were detected among 40 neurosyphilis patients, 31 syphilis/non-neurosyphilis patients, 26 non-syphilis/other central nervous system diseases patients. Serum CXCL13 concentrations were detected in 49 healthy persons. All enrolled persons were HIV-negative. Receiver operating characteristic (ROC) analysis was performed to determine the threshold value that could distinguish neurosyphilis from syphilis. We found that the CSF CXCL13 concentrations and CXCL13 quotient (QCXCL13) were significantly increased in neurosyphilis patients compared to syphilis/non-neurosyphilis (χ2 = 21.802, P < 0.001) and non-syphilis patients (χ2 = 7.677, P = 0.002). ROC curve analyses revealed that CSF CXCL13 concentrations and QCXCL13 could serve as valuable biomarkers for differentiating neurosyphilis from non-neurosyphilis/syphilis. The CSF CXCL13 and QCXCL13 could serve as valuable biomarkers for differentiating neurosyphilis from non-neurosyphilis/syphilis in HIV-negative patients.

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 ([email protected] 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 [email protected] NPs can enhance light absorption and achieve a better photothermal effect than bismuth NPs. Moreover, after irradiation under an 808 nm laser, the [email protected] NPs can efficiently induce the generation of reactive oxygen species (ROS), thereby synergizing PDT/PTT to exert an efficient tumor ablation effect both in vitro and in vivo. Furthermore, [email protected] NPs can also be employed to perform enhanced CT/PA imaging because of their high X-ray absorption attenuation and enhanced photothermal conversion. Thus, they can be utilized as a highly effective CT/PA imaging-guided nanotheranostic agent. In addition, an excellent antibacterial effect was achieved. After irradiation under an 808 nm laser, the [email protected] NPs can destroy the integrity of Escherichia coli, thereby inhibiting E. coli growth, which can minimize the risk of infection during cancer therapy. In conclusion, our study provides a novel nanotheranostic platform that can achieve CT/PA-guided PDT/PTT synergistic therapy and have potential antibacterial properties. Thus, this work provides an effective strategy for further broad clinical application prospects.

In the last decade, the biosynthesis of metal nanoparticles using organisms have received more and more considerations. However, the complex composition of organisms adds up to a great barrier for the characterization of biomolecules involved in the synthesis process and their biological mechanisms. In this research, we biosynthesized a kind of flower-shaped Au nanoclusters (Au NCs) using one definite component—epigallocatechin gallate (EGCG), which was the main biomolecules of green tea polyphenols. Possessing good stability for 6 weeks and a size of 50 nm, the Au NCs might be a successful candidate for drug delivery. Hence, both methotrexate (MTX) and doxorubicin (DOX) were conjugated to the Au NCs through a bridge of cysteine (Cys). The introduction of MTX provided good targeting property for the Au NCs, and the conjugation of DOX provided good synergistic effect. Then, a novel kind of dual-drug loaded, tumor-targeted and highly efficient drug delivery system (Au-Cys-MTX/DOX NCs) for combination therapy was successfully prepared. The TEM of HeLa cells incubated with Au-Cys-MTX/DOX NCs indicated that the Au-Cys-MTX/DOX NCs could indeed enter and kill cancer cells. The Au-Cys-MTX/DOX NCs also possessed good targeting effect to the FA-receptors-overpressed cancer cells both in vitro and in vivo. Importantly, the Au-Cys-MTX/DOX NCs resulted in an excellent anticancer activity in vivo with negligible side effects. These results suggest that the biosynthesized Au-Cys-MTX/DOX NCs could be a potential carrier with highly efficient anticancer properties for tumor-targeted drug delivery.