Dual-targeted and dual-sensitive self-assembled protein nanocarrier delivering hVEGI-192 for triple-negative breast cancer.

Breast cancer is a highly prevalent malignancy worldwide among women with an increasing incidence in recent years. Triple-negative breast cancer (TNBC), a specific type of breast cancer, occurs primarily in young women and exhibits large tumor size, high clinical stage, and extremely poor prognosis with a high rate of lymph node, liver, and lung metastases. TNBC is insensitive to endocrine therapy and trastuzumab treatment, and there is an urgent need for effective therapeutics and treatment guidelines. However, investigations into antiangiogenic agents for the treatment of TNBC are ongoing. In this study, we successfully engineered a self-assembled protein nanocarrier TfRBP9-hVEGI-192-ELP fusion protein (TVEFP) to deliver the therapeutic protein, human vascular endothelial growth inhibitor (hVEGI-192). This was found to be effective in inhibiting tumor angiogenesis in vivo. The protein nanocarrier effectively inhibited the progression of TNBC in vivo and showed the behavior of self-assembly, thermoresponsiveness, enzyme stimulation-responsiveness, tumor-targeting, biocompatibility, and biodegradability. Near-infrared imaging studies showed that fluorescent dye-stained TVEFP effectively aggregated at the tumor site. The TVEFP nanocarrier significantly expands the application of the therapeutic protein hVEGI-192 and improves the imaging and biotherapeutic effects in TNBC, chiefly based on anti-angiogenesis effects.

A simple and programmable dual-mode aptasensor for the ultrasensitive detection of multidrug-resistant bacteria.

Accurately identifying multidrug-resistant (MDR) bacteria from clinical samples has long been a challenge. Herein, we report a simple and programmable dual-mode aptasensor called DAPT to reliably detect MDR bacteria. The DAPT method comprises two elements, namely the mode of dynamic light scattering (Mode-DLS) for ultrasensitive detection and the mode of fluorescence (Mode-Flu) for reliable quantification as a potent complement. Benefiting from the states of aptamer-modified gold nanoparticles (AptGNPs) sensitively changing from dispersion to aggregation, the proposed Mode-DLS achieved the rapid, specific, and ultrasensitive detection of methicillin-resistant Staphylococcus aureus (MRSA) at the limit of detection (LOD) of 4.63 CFU mL-1 in a proof-of-concept experiment. Simultaneously, the Mode-Flu ensured the accuracy of the detection, especially at a high concentration of bacteria. Moreover, the feasibility and universality of the DAPT platform was validated with four other superbugs by simply reprogramming the corresponding sequence. Overall, the proposed DAPT method based on a dual-mode aptasensor can provide a universal platform for the rapid and ultrasensitive detection of pathogenic bacteria due to its superior programmability.

High expression of CLEC10A in head and neck squamous cell carcinoma indicates favorable prognosis and high-level immune infiltration status.

Immunotherapy has emerged as a promising treatment modality for HNSCC. However, only a small proportion of HNSCC patients experience clinical benefits from immunotherapy and identifying molecular markers that can serve as effective prognostic signatures and predictive indicators for immunotherapy response in patients with HNSCC is critical. CLEC10A has attracted attention because of its important role in improving the antitumor activity of immune cells. However, to our knowledge, no study has evaluated the role of CLEC10A in HNSCC prognosis, progression, and immune microenvironment. In the present study, we comprehensively analyzed expression profiles of CLEC10A and its association with tumor progression, HPV status, and survival of patients. Moreover, we explored the association between CLEC10A expression relative to immune infiltration and the response to immunotherapy. We explored the association between the timing of the receipt of palliative care relative to cancer diagnosis and survival. Our results revealed that CLEC10A has decreased expression in HNSCC compared with normal tissues, and that low expression of CLEC10A was associated with an advanced clinical stage and poor prognosis. Furthermore, a higher level of CLEC10A expression correlated with immune infiltration presence and response to immunotherapy in HNSCC. Thus, we demonstrated that CLEC10A could be a potential prognostic marker in patients with HNSCC, and a potential target for immunotherapy.