Vancomycin-Loaded Nanoparticles Enhance Sporicidal and Antibacterial Efficacy for Clostridium difficile Infection

Current antibiotic treatments fail to eliminate the Clostridium difficile (C. difficile) spores and induce dysbiosis and intestinal inflammation via off-target effect, which causes refractory C. difficile infection raise an unmet need for a spore-specific antimicrobial treatment. We developed a sporicidal and antimicrobial vancomycin-loaded spore-targeting iron oxide nanoparticle (van-IONP) that selectively binds to C. difficile spores. Cryo-electron microscopy showed that vancomycin-loaded nanoparticles can target and completely cover spore surfaces. They not only successfully delayed the germination of the spores but also inhibited ∼50% of vegetative cell outgrowth after 48 h of incubation. The van-IONPs also inhibited the interaction of spores with HT-29 intestinal mucosal cells in vitro. In a murine model of C. difficile infection, the van-IONP significantly protected the mice from infected by C. difficile infection, reducing intestinal inflammation, and facilitated superior mucosal viability compared with equal doses of free vancomycin. This dual-function targeted delivery therapy showed advantages over traditional therapeutics in treating C. difficile infection

_In vivo_ photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods

The use of gold nanorods for photoacoustic molecular imaging in vivo with simultaneous multiple selective targeting is reported. The extravasation of multiple molecular probes is demonstrated, and used to probe molecular information of cancer cells. This technique allows molecular profiles representing tumor characteristics to be obtained and a heterogeneous population of cancer cells in a lesion to be determined. The results also show that the image contrast can be enhanced by using a mixture of different molecular probes. In this study, HER2, EGFR, and CXCR4 were chosen as the primary target molecules for examining two types of cancer cells, OECM1 and Cal27. OECM1 cells overexpressed HER2 but exhibited a low expression of EGFR, while Cal27 cells showed the opposite expression profile. Single and double targeting resulted in signal enhancements of up to 3 dB and up to 5 dB, respectively, and hence has potential in improving cancer diagnoses

Opportunities for Nanomedicine in Clostridioides difficile Infection

Clostridioides difficile, a spore-forming bacterium, is a nosocomial infectious pathogen which can be found in animals as well. Although various antibiotics and disinfectants were developed, C. difficile infection (CDI) remains a serious health problem. C. difficile spores have complex structures and dormant characteristics that contribute to their resistance to harsh environments, successful transmission and recurrence. C. difficile spores can germinate quickly after being exposed to bile acid and co-germinant in a suitable environment. The vegetative cells produce endospores, and the mature spores are released from the hosts for dissemination of the pathogen. Therefore, concurrent elimination of C. difficile vegetative cells and inhibition of spore germination is essential for effective control of CDI. This review focused on the molecular pathogenesis of CDI and new trends in targeting both spores and vegetative cells of this pathogen, as well as the potential contribution of nanotechnologies for the effective management of CDI

From Microenvironment Remediation to Novel Anti-Cancer Strategy: The Emergence of Zero Valent Iron Nanoparticles

Accumulated studies indicate that zero-valent iron (ZVI) nanoparticles demonstrate endogenous cancer-selective cytotoxicity, without any external electric field, lights, or energy, while sparing healthy non-cancerous cells in vitro and in vivo. The anti-cancer activity of ZVI-based nanoparticles was anti-proportional to the oxidative status of the materials, which indicates that the elemental iron is crucial for the observed cancer selectivity. In this thematic article, distinctive endogenous anti-cancer mechanisms of ZVI-related nanomaterials at the cellular and molecular levels are reviewed, including the related gene modulating profile in vitro and in vivo. From a material science perspective, the underlying mechanisms are also analyzed. In summary, ZVI-based nanomaterials demonstrated prominent potential in precision medicine to modulate both programmed cell death of cancer cells, as well as the tumor microenvironment. We believe that this will inspire advanced anti-cancer therapy in the future

Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand

Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL

Involvement of gelsolin in TGF-beta 1 induced epithelial to mesenchymal transition in breast cancer cells

Increasing evidence suggests that transforming growth factor-beta 1 (TGF-β1) triggers epithelial to mesenchymal transition (EMT) and facilitates breast cancer stem cell differentiation. Gelsolin (GSN) is a ubiquitous actin filament-severing protein. However, the relationship between the expression level of GSN and the TGF-β signaling for EMT progression in breast cancer cells is not clear