Pro-apoptotic and size-reducing effects of protein corona-modulating nano-architectures enclosing platinum prodrug in in vivo oral carcinoma

: The selective and localized delivery of active agents to neoplasms is crucial to enhance the chemotherapeutic efficacy while reducing the associated side effects. The encapsulation of chemotherapeutics in nanoparticles decorated with targeting agents is a strategy of special interest to improve drug delivery. However, serum protein adsorption often compromises the in vivo efficiency of targeting agents, leading to protein corona formation that interferes with the targeting process. Here, the enhanced efficacy of hybrid nano-architectures enclosing a platinum prodrug and decorated with a customized peptide (NAs-cisPt-Tf2) is demonstrated by employing alternative in vivo models of oral carcinoma. The peptide binds to transferrin and modulates the protein corona formation on NAs-cisPt-Tf2, supporting the identification of its receptor. Optimized chorioallantoic membrane cancer models (CAMs) enabled a thorough assessment of the tumor-suppressing effect of NAs-cisPt-Tf2 as well as the quantitative evaluation of angiogenesis and cell cycle associated mechanisms. The treatment strategy resulted in a significant tumor volume reduction coupled with anti-angiogenic and pro-apoptotic effects inferred from the downregulation of the vascular endothelial growth factor gene and increased expression of cleaved caspase-3. Overall, this study provides a potentially effective tumor-targeted approach for a non-invasive management of oral carcinoma

Total- and semi-bare noble metal nanoparticles@silica core@shell catalysts for hydrogen generation by formic acid decomposition

AbstractCatalysts are involved in a number of established and emerging chemical processes as well as in environmental remediation and energy conversion. Nanoparticles (NPs) can offer several advantages over some conventional catalysts, such as higher efficiency and selectivity. Nowadays, versatile and scalable nanocatalysts that combine activity and stability are still lacking. Here, we report a comprehensive investigation on the production and characterization of hybrid nano-architectures bringing a partial or total bare surface together with their catalytic efficiency evaluation on, as a proof-of-concept, the formic acid decomposition reaction. In this regard, formic acid (FA) is a convenient and safe hydrogen carrier with appealing features for mobile applications, fuel cells technologies, petrochemical processes and energetic applications. Thus, the design of robust catalysts for FA dehydrogenation is strongly demanded. Due to this, we produced and evaluated nano-architectures with various equilibrium between the size-increase of the active part and the barer catalytic surface. Overall, this work paves the way for the development of new approaches for green energy storage and safe delivery

Drug-Free Hybrid Nanoarchitecture Modulation of the Metastatic Behavior of Pancreatic Ductal Adenocarcinoma in Alternative in Vivo Models

Metastasis is the key cause of treatment failure in most oncological patients. The spreading of cancer cells to distal tissues and organs can be associated with the epithelial-to-mesenchymal transition (EMT) that reduces or nullifies the effectiveness of the actual treatments. In this context, the establishment of effective antimetastatic agents is the final frontier in cancer research. Noble metal nanomaterials may allow advancements in this regard, but the issue of their persistence precludes their translation to clinics despite their antimetastatic properties. Here, we demonstrate that non-persistent gold and copper ultrasmall-in-nano architectures (NAs) conceived by a safe-by-design approach reduce tumor growth and modulate the progression of the metastasis by altering gene and protein expression of the EMT-related factors in alternative in vivo models of pancreatic ductal adenocarcinoma. Together with these findings, we also introduce an alternative biomodel for the evaluation of metastasis to mimic the heterogeneity of the metastatic phenomenon. On a broader basis, our results represent a promising step forward in the development of novel families of ultrasmall-in-nano antimetastatic agents for the establishment of the next clinical approaches for pancreatic cancer metastasis

Antibody drug conjugates with hydroxamic acid cargos for histone deacetylase (HDAC) inhibition.

The bioconjugation of hydroxamic acids to antibodies has been made possible through a non-cleavable linker based on the p-mercaptobenzyl alcohol structure that releases hydroxamates in the cells

Surface Nanostructuring For Surface Plasmon Resonance Imaging

Improving the performances of a sensor is a prominent objective in developing innovative for clinical applications. Sensitivity is key features for a biosensor such applications. An improvement in sensitivity is reported when nanoparticles (NPs) are exploited for functionalizing the interacting surface. In this work an original nanostructure was investigated. Gold nanoparticles are immobilized on a gold surface of a Surface Plasmon Resonance imaging (SPRi) sensor. The surface structuring strategy was studied in its steps, for obtaining a reproducible immobilization of NPs on biochip gold surface. In order to improve our system, we modified SPRi chip with gold NPs attached on the surface trough a dithiol molecule. Further functionalization was achieved using thiolated DNA probes. The possibility to modify the biochip in an array format was really helpful for following the different steps of the procedure. The bioreceptors immobilization protocol was studied following the plasmon curves, confirming the presence of the nanostructure on the biochip surface. © 2011 IEEE

Bioanalytical approaches for the detection of single nucleotide polymorphisms by Surface Plasmon Resonance biosensors

In this review, Surface Plasmon Resonance (SPR) and Surface Plasmon Resonance imaging (SPRi) biosensors applied to the recognition of SNPs were reviewed, since these technologies are emerging in clinical diagnosis as powerful tools thanks to their analytical features, mainly the real-time and label-free monitoring based on array format for parallel analysis. Since the literature is heterogeneous, a critical classification and a systemic comparison of the analytical performances of published methods were here reviewed on the basis of the analytical strategy and the assay design. In particular, the use of helping agents (i.e. proteins, nanoparticles (NPs), intercalating agents) or artificial DNAs, often coupled to SPR to achieve allele discrimination and/or enhanced sensitivity, were here revised and classified. Finally, the real suitability of SPR biosensors to clinical diagnostics for SNPs detection was addressed by comparing their features and performances with those of other biosensors based on other techniques (e.g. electrochemical biosensors)

Surface Plasmon Resonance Imaging For Affinity-Based Sensing: An Analytical Approach

Surface Plasmon Resonance imaging (SPRi) is at the forefront of optical sensing, allowing multi-analyte detection in real-time and without labeling. SPRi is applied to a variety of bio-interactions, from proteins to sensitive DNA detection. Despite the high number of recently appeared papers, very few deal with analyte detection in complex matrices. We here report SPRi affinity-based sensing with application to analytes detection in real matrices, i.e. proteins and DNA marker sequences for possible applications in different fields. In particular, we quantified Bovine IgG in cow milk avoiding matrix pre-treatments, and showing the simultaneous evaluation of different immobilization chemistries on a single biochip. We summarize results obtained in terms of perspectives for a real application of the biosensor in the field of food controls. About the detection of DNA sequences in complex matrices, we focused on DNA sequences in human transgenic cells for gene doping controls. Experimental results are briefly showed here in terms of advantages related to the application of SPRi technique to this emerging issue. © 2011 IEEE

Investigating nanoparticle properties in plasmonic nanoarchitectures with DNA by surface plasmon resonance imaging

Nanoparticles with different sizes, refractive indices and plasmonic profiles are synthesized, labelled with DNA and embedded in DNA-based plasmonic nanoarchitectures. The contribution of the different properties to reflectivity variation % is rationally investigated by DNA hybridization measurements using the surface plasmon resonance imaging (SPRi) technology