A novel fundamental understanding of the features of mechanism for the synthesis of luminescent silver nanoclusters (AgNCs) in human hemoglobin (Hb) as capping/reducing agents is presented based upon simultaneous size transition and fluorescence enhancement phenomena  The interesting features consist of both NC core oxidation and aggregation-induced emission (AIE) attributed to ligand-to-metal charge transfer (LMCT) or ligand-to-metal–metal charge transfer (LMMCT) from Ag­(I)-Hb complexes (through oxygen, nitrogen, and sulfur atoms of Hb residues donation to the Ag­(I) ions) forming Ag(0)@Ag­(I)–Hb core–shell NCs, the origin and consequence being a dual emission/single excitation nanosystem with large stocks shift and high quantum yield obtained even at high temperature which is a challenging subject,  is not reported until now. The bioconjugation of hyaluronic acid (HA) onto surfaces of an Hb layer (HA/AgNCs) produced a biocompatible platform with a doxorubicin drug (DOX) as DOX/HA/AgNCs for specific imaging and delivery of DOX via an efficient targeting of CD44-overexpressing cancer cells, which lead to an increased inhibition of tumor cell growth. Additionally, the cell viability analysis illustrated that the developed nanocarriers significantly enhanced the DOX uptake in HeLa cancer cells compared to HUVEC and HNCF-PI 52 normal cells allowing a selective cytotoxicity to HeLa cells. The suggested LMCT/LMMCT mechanism for an emission source combined with such attractive properties as a simple one-pot, nontoxic, synthesis route, long lifetime, large Stocks shift, excellent aqueous stability and photostability, and easy functionalization capability with good cell viability provided the possibility for a AgNCs nanoprobe for use to better understand the nucleation and growth mechanisms via computational modeling techniques (e.g., DFT study) and also for fabrication of new nanoprobes for developing multifunctional applications in the biobased chemical and electrochemical fields and in in vivo research.

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Microfluidics cell-based assays require strong cell-substrate adhesion for cell viability, proliferation, and differentiation. The intrinsic properties of PDMS, a commonly used polymer in microfluidics systems, regarding cell-substrate interactions have limited its application for microfluidics cell-based assays. Various attempts by previous researchers, such as chemical modification, plasma-treatment, and protein-coating of PDMS revealed some improvements. These strategies are often reversible, time-consuming, short-lived with either cell aggregates formation, not cost-effective as well as not user- and eco-friendly too. To address these challenges, cell-surface interaction has been tuned by the modification of PDMS doped with different biocompatible nanomaterials. Gold nanowires (AuNWs), superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide sheets (GO), and graphene quantum dot (GQD) have already been coupled to PDMS as an alternative biomaterial enabling easy and straightforward integration during microfluidic fabrication. The synthesized nanoparticles were characterized by corresponding methods. Physical cues of the nanostructured substrates such as Young’s modulus, surface roughness, and nanotopology have been carried out using atomic force microscopy (AFM). Initial biocompatibility assessment of the nanocomposites using human amniotic mesenchymal stem cells (hAMSCs) showed comparable cell viabilities among all nanostructured PDMS composites. Finally, osteogenic stem cell differentiation demonstrated an improved differentiation rate inside microfluidic devices. The results revealed that the presence of nanomaterials affected a 5- to 10-fold increase in surface roughness. In addition, the results showed enhancement of cell proliferation from 30% (pristine PDMS) to 85% (nano-modified scaffolds containing AuNWs and SPIONs), calcification from 60% (pristine PDMS) to 95% (PDMS/AuNWs), and cell surface marker expression from 40% in PDMS to 77% in SPION- and AuNWs-PDMS scaffolds at 14 day. Our results suggest that nanostructured composites have a very high potential for stem cell studies and future therapies.

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Host defense peptides selectively kill bacterial and cancer cells (including those that are drugresistant) by perturbing the permeability of their membranes, without being significantly toxic to the host. Coulombic interactions between these cationic and amphipathic peptides and the negatively charged membranes of pathogenic cells contribute to the selective toxicity. However, a positive charge is not sufficient for selectivity, which can be achieved only by a finely tuned balance of electrostatic and hydrophobic driving forces. A common property of amphipathic peptides is the formation of aggregated structures in solution, but the role of this phenomenon in peptide activity and selectivity has received limited attention. Our data on the anticancer peptide killerFLIP demonstrate that aggregation strongly increases peptide selectivity, by reducing the effective peptide hydrophobicity and thus the affinity towards membranes composed of neutral lipids (like the outer layer of healthy eukaryotic cell membranes). Aggregation is therefore a useful tool to modulate the selectivity of membrane active peptides and peptidomimetics.

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