Rapid nucleation and optimal surface-ligand interaction stabilize wurtzite MnSe.

Non-native structures (NNS) differ in discrete translational symmetry from the bulk ground state native structure (NS). To explore the extent of deconvolution of various factors relevant to the stabilization of the wurtzite/NNS of MnSe via a heat-up method, we performed experiments using various ligands (oleic acid, oleylamine, octadecylamine, stearic acid, and octadecene), solvents (tetraethylene glycol and octadecene), and precursor salts (manganese chloride and manganese acetate). Experiments suggest that oleic acid in the presence of tetraethylene glycol and oleylamine in the presence of octadecene stabilize wurtzite/NNS. Further, density functional theory (DFT) computations explore the interaction between the functional groups in ligands and the most exposed surfaces of wurtzite/NNS and rocksalt/NS polymorphs. Computations suggest that the interactions between relevant surface facets with carboxylic acid and the double bond functional groups suppress the phase transformation from NNS to NS. In addition, the ionizability of the precursor salt also determines the rate of formation of the metal-ligand complex and the rate of nucleation. Consequently, the formation rate of the Mn-ligand complex is expected to be greater in the case of chloride salt than acetate salt because the chloride salt has higher ionizability in ethylene glycol. From the above, we conclude that the kinetics of the wurtzite/NNS to rocksalt/NS phase transformation depends mainly on two factors: (1) nucleation/growth kinetics which is controlled by the ionizability of the precursor salt, solvent, and stability of the metal-ligand complex, and (2) the activation energy barrier of the NNS to NS conversion which is controlled by surface energy minimization with the ligand.

Resveratrol-Ampicillin Dual-Drug Loaded Polyvinylpyrrolidone/Polyvinyl Alcohol Biomimic Electrospun Nanofiber Enriched with Collagen for Efficient Burn Wound Repair.

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries. Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair. Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10. Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.

3D Characterization of the Aortic Valve and Aortic Arch in Bicuspid Aortic Valve Patients.

Patients with bicuspid aortic valve (BAV) commonly have associated aortic stenosis and aortopathy. The geometry of the aortic arch and BAV is not well defined quantitatively, which makes clinical classifications subjective or reliant on limited 2D measurements. The goal of this study was to characterize the 3D geometry of the aortic arch and BAV using objective and quantitative techniques. Pre-TAVR computed tomography angiogram (CTA) in patients with BAV and aortic stenosis (AS) were analyzed (n = 59) by assessing valve commissural angle, presence of a fused region, percent of fusion, and calcium volume. The ascending aorta and aortic arch were reconstructed from patient-specific imaging segmentation to generate a centerline and calculate maximum curvature and maximum area change for the ascending aorta and the descending aorta. Aortic valve commissural angle signified a bimodal distribution suggesting tricuspid-like (≤ 150°, 52.5% of patients) and bicuspid-like (> 150°, 47.5%) morphologies. Tricuspid like was further classified by partial (10.2%) or full (42.4%) fusion, and bicuspid like was further classified into valves with fused region (27.1%) or no fused region (20.3%). Qualitatively, the aortic arch was found to have complex patient-specific variations in its 3D shape with some showing extreme diameter changes and kinks. Quantitatively, subgroups were established using maximum curvature threshold of 0.04 and maximum area change of 30% independently for the ascending and descending aorta. These findings provide insight into the geometric structure of the aortic valve and aortic arch in patients presenting with BAV and AS where 3D characterization allows for quantitative classification of these complex anatomic structures.

Chiral nanomaterial-based approaches for diagnosis and treatment of protein-aggregated neurodiseases: current status and future opportunities.

Protein misfolding and its aggregation, known as amyloid aggregates (Aß), are some of the major causes of more than 20 diseases such as Parkinson's disease, Alzheimer's disease, and type 2 diabetes. The process of Aß formation involves an energy-driven oligomerization of Aß monomers, leading to polymerization and eventual aggregation into fibrils. Aß fibrils exhibit multilevel chirality arising from its amino acid residues and the arrangement of folded polypeptide chains; thus, a chirality-driven approach can be utilized for the detection and inhibition of Aß fibrils. In this regard, chiral nanomaterials have recently opened new possibilities for various biomedical applications owing to their stereoselective interaction with biological systems. Leveraging this chirality-driven approach with chiral nanomaterials against protein-aggregated diseases could yield promising results, particularly in the early detection of Aß forms and the inhibition of Aß aggregate formation via specific and strong "chiral-chiral interaction." Despite the advantages, the development of advanced theranostic systems using chiral nanomaterials against protein-aggregated diseases has received limited attention so far because of considerably limited formulations for chiral nanomaterials and lack of information of their chiroptical behavior. This review aims to present the current status of chiral nanomaterials explored for detecting and inhibiting Aß forms. This review covers the origin of chirality in amyloid fibrils and nanomaterials and different chiral detection methods; furthermore, different chiral nanosystems such as chiral plasmonic nanomaterials, chiral carbon-based nanomaterials, and chiral nanosurfaces, which have been used so far for different therapeutic applications against protein-aggregated diseases, are discussed in detail. The findings from this review may pave the way for the development of novel approaches using chiral nanomaterials to combat diseases resulting from protein misfolding and can further be extended to other disease forms.

PDMS nanoparticles-decorated PDMS substrate promotes adhesion, proliferation and differentiation of skin cells.

Polydimethylsiloxane (PDMS) is known to be a common substrate for various cell culture-based applications. However, native PDMS is not very conducive for cell culture and hence, surface modification via cell adhesion moieties is generally needed to make it suitable especially for long-term cell culture. To address this issue, we propose to coat PDMS nanoparticles (NPs) on the surface of PDMS film to improve adhesion, proliferation and differentiation of skin cells. The proposed modification strategy introduces necessary nanotopography without altering the surface chemical properties of PDMS. Due to resemblance in the mechanical properties of PDMS with skin, PDMS NPs can recreate the native extracellular nanoenvironment of skin on the PDMS surface and provide anchoring sites for skin cells to adhere and grow. Human keratinocytes, representing 95% of the epidermal skin cells maintained their characteristic well-spread morphology with the formation of interconnected cell-sheets on this coated PDMS surface. Moreover, our in vitro immunofluorescence studies confirmed expression of distinctive epidermal protein markers on the coated surface indicating close resemblance with the native skin epidermis. Conclusively, our findings suggest that introducing nanotopography via PDMS NPs can be an effective strategy for emulating the native cellular functions of keratinocytes on PDMS based cell culture devices.

Tetragonal-zircon BiVO4: a better polymorph for the formation of coherent type-II heterostructures for water splitting applications.

The monoclinic-scheelite (m-s) polymorph of BiVO4 has the highest photocatalytic activity, whereas tetragonal-zircon (t-z) has the lowest photocatalytic activity, which may be due to a higher band gap. However, t-z has the highest crystal symmetry, which makes it a more suitable candidate to form coherent type-II interfaces for the efficient separation of electron-hole pairs. Furthermore, the method of preparation (e.g. low temperature and moderate pH) of t-z is more facile compared to the m-s polymorph. Hence, in this report, we construct coherent isomaterial and heteromaterial type-II heterostructures by facet engineering of low index surfaces of t-z polymorph with different semiconductor materials (e.g. ZnO, TiO2, CdSe, and ZnS) by screening the band gap, band edge positions, and lattice misfit strain. On the basis of the calculated band-edge positions, the polymorphs of BiVO4 can form 212 combinations of the type-II interface, which reduces to 17 coherent interfaces with lattice misfit strain between 1.55% to 28.5% when translational symmetry, atomic positions, lattice mismatch, and bond complementarity have been imposed. Furthermore, the current study suggests that t-z polymorphs can form more coherent interfaces (4 out of 168), which may be due to its highest symmetry structure in comparison to previously formed 67 isomaterial and heteromaterial type-II heterostructure combinations of BiVO4 (1 out of 67), which suggests that t-z can be a suitable candidate for the formation of type-II coherent interfaces for PEC/PC applications.

Calcium Fracture and Device Over Expansion in Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves.

Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve disease (BAV) has potential risks of under expansion and non-circularity which may compromise long-term durability. This study aims to investigate calcium fracture and balloon over expansion in balloon-expandable TAVs on the stent deformation with the aid of simulation. BAV patients treated with the SAPIEN 3 Ultra with pre- and post-TAVR CTs were analyzed (n = 8). Simulations of the stent deployment were performed (1) with baseline simulation allowing calcium fracture, (2) without allowable calcium fracture and (3) with balloon over expansion (1 mm larger diameter). When compared to post CT, baseline simulations had minimal error in expansion (2.5% waist difference) and circularity (3.0% waist aspect ratio difference). When compared to baseline, calcium fracture had insignificant impact on the expansion (- 0.5% average waist difference) and circularity (- 1.6% average waist aspect ratio difference). Over expansion had significantly larger expansion compared to baseline (15.4% average waist difference) but had insignificant impact on the circularity (- 0.5% waist aspect ratio difference). We conclude that stent deformation can be predicted with minimal error, calcium fracture has small differences on the final stent deformation except in extreme calcified cases, and balloon over expansion expands the waist closer to nominal values.

Quaternary Ru(II) complexes of terpyridines, saccharin and 1,2-azoles: effect of substituents on molecular structure, speciation, photoactivity, and photocytotoxicity.

Six photoactive ruthenium quaternary complexes (a four-component system consisting of three different N-donor ligands and Ru(II)): trans-[Ru(R-tpy)(pyz/ind)(sac)2] (1-6) containing substituted terpyridine (R-tpy), saccharin (sac), and monodentate N-donor heterocycles were designed. Here, R-tpy = 4'-(2-furyl (1, 2); thienyl (3, 4); pyridyl (5, 6))-2,2':6',2'' terpyridines, pyz = 1H-pyrazole for 1, 3 and 5 and ind = 1H-indazole for 2, 4 and 6. The azoles are present in a large number of FDA-approved clinical drugs and bioactive molecules. The saccharin acting as a carbonic anhydrase inhibitor (CA-IX) could potentially target aggressive hypoxic tumors that overexpress CA-IX. Such multi-functional ligands bound to a Ru(II)-photocage provide ample scope to tune the electronic structures, photochemistry, and synergistic effect of the photolabile ligands in photoactivated chemotherapy (PACT). The complexes were characterized using various spectroscopic studies, and the molecular structures were determined from X-ray crystallography. They exhibit a distorted octahedral {RuN6} geometry with equatorial sites coordinated to the tridentate N3-donor R-tpy and N-donor pyz/ind, while two transoidal axial sites bound to the N-donor saccharinate (sac) ligands. The solvolysis kinetics showed these complexes undergo facile ligand-exchange reactions in equilibrium with varying rates reflecting the possible electronic effect of the R-groups in R-tpy. The photoreactivity of the complexes in green (λex = 530 nm) LED light indicates that the complexes undergo photodissociation of the monodentate N-donors (i.e., sac/pyz/ind) and showed an efficient generation of singlet oxygen (Φ1O2 = 0.29-0.47), signifying the potential of these complexes in PACT and/or PDT. All the complexes show good binding affinity with CT-DNA with possible intercalation from extended planar polypyridyl ligands with duplex DNA and BSA. The synchronous fluorescence study with BSA suggested preferential interaction at the tryptophan residue in the protein microenvironment. The confocal microscopy studies showed adequate permeability and localization in the cytosol and nucleus of cervical cancer (HeLa) and breast cancer (MCF7) cells. The dose-dependent cytotoxicity of the complexes for both HeLa and MCF7 cells increases upon low-energy (365 nm) photoirradiation. The mechanistic studies revealed that the complexes induce apoptosis and generate reactive oxygen species (ROS) upon green light (λex = 530 nm) irradiation. Overall, these quaternary Ru(II) complexes equipped with three different types of ligands with distinct roles could pave the way for designing multi-targeted chemotherapeutic metallodrugs with synergistic roles for each bioactive ligand.

Investigating the photosensitivity of koneramines for cell imaging and therapeutic applications.

The photophysical properties of the anthracene appended koneramines (LAn) were analyzed and utilized as a chemosensor for the selective detection of Cd2+ and Zn2+. The complexation-induced inhibition of PET (photo-induced electron transfer) from the chelating nitrogen atoms to the excited state of the anthracene moiety resulted in a fluorescence "turn-on" signal upon binding with Cd2+ and Zn2+. The confocal microscopic imaging studies performed on the MCF-7 cells validated that the compound is potentially useful for detecting Cd2+ and Zn2+ inside the cells. The cadmium complex exhibited unique bactericidal activity against clinically relevant human pathogens. The excellent activity against multidrug-resistant S. aureus makes the complex useful as a new, easily synthesizable antibiotic. The cadmium complex LAnCdCl2 was not cytotoxic against vero cells with a selectivity index of 40, exhibited concentration dependent bactericidal killing, was non-interactive with several other clinically approved standard drugs, exhibited prolonged post-antibiotic effect (PAE) against S. aureus ATCC 29213 and possesses antibiofilm activity.

A simple, robust and scalable route to prepare sub-50 nm soft PDMS nanoparticles for intracellular delivery of anticancer drugs.

Soft nanoparticles (NPs) have recently emerged as a promising material for intracellular drug delivery. In this regard, NPs derived from polydimethylsiloxane (PDMS), an FDA approved polymer can be a suitable alternative to conventional soft NPs due to their intrinsic organelle targeting ability. However, the available synthesis methods of PDMS NPs are complicated or require inorganic fillers, forming composite NPs and compromising their native softness. Herein, for the first time, we present a simple, robust and scalable strategy for preparation of virgin sub-50 nm PDMS NPs at room temperature. The NPs are soft in nature, hydrophobic and about 30 nm in size. They are stable in physiological medium for two months and biocompatible. The NPs have been successful in delivering anticancer drug doxorubicin to mitochondria and nucleus of cervical and breast cancer cells with more than four-fold decrease in IC50 value of doxorubicin as compared to its free form. Furthermore, evaluation of cytotoxicity in reactive oxygen species detection, DNA fragmentation, apoptosis-associated gene expression and tumor spheroid growth inhibition demonstrate the PDMS NPs to be an excellent candidate for delivery of anticancer drugs in mitochondria and nucleus of cancer cells.

Image Registration-Based Method for Reconstructing Transcatheter Heart Valve Geometry from Patient-Specific CT Scans.

Accurate reconstruction of transcatheter aortic valve (TAV) geometries and other stented cardiac devices from computed tomography (CT) images is challenging, mainly associated with blooming artifacts caused by the metallic stents. In addition, bioprosthetic leaflets of TAVs are difficult to segment due to the low signal strengths of the tissues. This paper describes a method that exploits the known device geometry and uses an image registration-based reconstruction method to accurately recover the in vivo stent and leaflet geometries from patient-specific CT images. Error analyses have shown that the geometric error of the stent reconstruction is around 0.1mm, lower than 1/3 of the stent width or most of the CT scan resolutions. Moreover, the method only requires a few human inputs and is robust to input biases. The geometry and the residual stress of the leaflets can be subsequently computed using finite element analysis (FEA) with displacement boundary conditions derived from the registration. Finally, the stress distribution in self-expandable stents can be reasonably estimated by an FEA-based simulation. This method can be used in pre-surgical planning for TAV-in-TAV procedures or for in vivo assessment of surgical outcomes from post-procedural CT scans. It can also be used to reconstruct other medical devices such as coronary stents.

Biomechanics of Transcatheter Aortic Valve Replacement Complications and Computational Predictive Modeling.

Transcatheter aortic valve replacement (TAVR) is a rapidly growing field enabling replacement of diseased aortic valves without the need for open heart surgery. However, due to the nature of the procedure and nonremoval of the diseased tissue, there are rates of complications ranging from tissue rupture and coronary obstruction to paravalvular leak, valve thrombosis, and permanent pacemaker implantation. In recent years, computational modeling has shown a great deal of promise in its capabilities to understand the biomechanical implications of TAVR as well as help preoperatively predict risks inherent to device-patient-specific anatomy biomechanical interaction. This includes intricate replication of stent and leaflet designs and tested and validated simulated deployments with structural and fluid mechanical simulations. This review outlines current biomechanical understanding of device-related complications from TAVR and related predictive strategies using computational modeling. An outlook on future modeling strategies highlighting reduced order modeling which could significantly reduce the high time and cost that are required for computational prediction of TAVR outcomes is presented in this review paper. A summary of current commercial/in-development software is presented in the final section.

Kinetically labile ruthenium(II) complexes of terpyridines and saccharin: effect of substituents on photoactivity, solvation kinetics, and photocytotoxicity.

Herein, we designed six kinetically labile ruthenium(ii) complexes containing saccharin (sac) and 4'-substituted-2,2':6',2''-terpyridines (R-tpy), viz. trans-[Ru(sac)2(H2O)3(dmso-S)] (1) and [RuII(R-tpy)(sac)2(X)] [X = solvent molecule] (2-6). We intentionally kept the labile hydrolysable Ru-X bonds that were potentially activated via solvent-exchange reactions. This strategy generates a coordinative vacancy that allows further binding with potential biological targets. To gain insight into the electronic effects of ancillary ligands on Ru-X ligand-exchange kinetics or photoreactions, we have used a series of substituted terpyridines (R-tpy) and studied their solvation kinetics. The ternary complexes were also studied for their potential utility in Ru-assisted photoactivated chemotherapy (PACT) synergized with release of saccharin as a highly selective carbonic anhydrase IX (CA-IX) inhibitor, over-expressed in hypoxic tumors. The ternary complexes exhibit distorted octahedral geometry around Ru(ii) from two monodentate transoidal saccharin in the axial position, and tridentate terpyridines and labile solvent molecules at the basal plane (2-6). We studied their speciation, solvation kinetics, and photoreactivity in the presence of green LED light (λirr = 530 nm). All the complexes are relatively labile and undergo solvation in coordinating solvents (e.g. DMSO/DMF). The complexes undergo the ligand-substitution reaction, and their speciation and kinetics were studied by UV-Vis, ESI-MS, 1H-NMR, and structural analysis. We also attempted to assess the effect of various substituents on the ancillary terpyridine ligand (R-tpy) in photo-reactivity and ligand-exchange reactions. The photo-induced absorption and emission measurements suggested dissociation of the saccharin from the Ru-center supporting PACT pathways. The complexes display a significant binding affinity with CT-DNA (Kb ∼ 104-105 M-1) and bovine serum albumin (BSA) (KBSA ∼ 105 M-1). Cytotoxicity was studied in the dark and the presence of low energy UV-A light (365 nm) in cervical cancer cells (HeLa) and breast cancer cells (MCF7). Photoirradiation of the complexes induces the generation of reactive oxygen species (ROS) assessed using 1,3-diphenylisobenzofuran (DPBF) and intracellular DCFDA assays. The complexes are sufficiently internalized in cancer cells throughout the cytoplasm and nucleus and induce apoptosis as studied by staining with dual dyes using confocal microscopy.

Blended polar/nonpolar peptide conjugate interferes with human insulin amyloid-mediated cytotoxicity.

Insulin, a peptide hormone and a key regulator of blood glucose level, is routinely administered to type-I diabetic patients to achieve the required glycemic control. Insulin aggregation and ensuing amyloidosis has been observed at repeated insulin injection sites and in injectable formulations. The latter occurs due to insulin agglomeration during shipping and storage. Such insulin amyloid leads to enhanced immunogenicity and allow potential attachment to cell membranes leading to cell permeability and apoptosis. Small molecule inhibitors provide useful interruption of this process and inhibit protein misfolding as well as amyloid formation. In this context, we report the propensity of a palmitoylated peptide conjugate to inhibit insulin aggregation and amyloid-mediated cytotoxicity, via designed interference with polypeptide interfacial interactions.

Luminescent lanthanide(III) complexes of DTPA-bis(amido-phenyl-terpyridine) for bioimaging and phototherapeutic applications.

We report here a series of coordinatively-saturated and thermodynamically stable luminescent [Ln(dtntp)(H2O)] [Ln(III) = Eu (1), Tb (2), Gd (3), Sm (4) and Dy (5)] complexes using an aminophenyl-terpyridine appended-DTPA (dtntp) chelating ligand as cell imaging and photocytotoxic agents. The N,N″-bisamide derivative of H5DTPA named as dtntp is based on 4'-(4-aminophenyl)-2,2':6',2″-terpyridine conjugated to diethylenetriamine-N,N',N″-pentaacetic acid. The structure, physicochemical properties, detailed photophysical aspects, interaction with DNA and serum proteins, and photocytotoxicity were studied. The intrinsic luminescence of Eu(III) and Tb(III) complexes due to f â†’ f transitions used to evaluate their cellular uptake and distribution in cancer cells. The solid-state structure of [Eu(dtntp)(DMF)] (1·DMF) shows a discrete mononuclear molecule with nine-coordinated {EuN3O6} distorted tricapped-trigonal prism (TTP) coordination geometry around the Eu(III). The {EuN3O6} core results from three nitrogen atoms and three carboxylate oxygen atoms, and two carbonyl oxygen atoms of the amide groups of dtntp ligand. The ninth coordination site is occupied by an oxygen atom of DMF as a solvent from crystallization. The designed probes have two aromatic pendant phenyl-terpyridine (Ph-tpy) moieties as photo-sensitizing antennae to impart the desirable optical properties for cellular imaging and photocytotoxicity. The photostability, coordinative saturation, and energetically rightly poised triplet states of dtntp ligand allow the efficient energy transfer (ET) from Ph-tpy to the emissive excited states of the Eu(III)/Tb(III), makes them luminescent cellular imaging probes. The Ln(III) complexes show significant binding tendency to DNA (K ~ 104 M-1), and serum proteins (BSA and HSA) (K ~ 105 M-1). The luminescent Eu(III) (1) and Tb(III) (2) complexes were utilized for cellular internalization and cytotoxicity studies due to their optimal photophysical properties. The cellular uptake studies using fluorescence imaging displayed intracellular (cytosolic and nuclear) localization in cancer cells. The complexes 1 and 2 displayed significant photocytotoxicity in HeLa cells. These results offer a modular design strategy with further scope to utilize appended N,N,N-donor tpy moiety for developing light-responsive luminescent Ln(III) bioprobes for theranostic applications.

Luminescent naphthalimide-tagged ruthenium(ii)-arene complexes: cellular imaging, photocytotoxicity and transferrin binding.

Two water-soluble piano-stool shaped ruthenium(ii)-arene complexes, [RuII(η6-p-cymene)(L)Cl2] [RuLCl] and [RuII(η6-p-cymene)(L)(PTA)Cl] [RuLPTA], were designed as emissive photocytotoxic agents tagged with morpholine as the lysosome targeting moiety. Here, L = N-(2-morpholinoethyl)-4-(2-aminoethyl)amino-naphthalimide, and PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane. The crystal structure of [RuLCl] exhibits the pseudooctahedral 'three-legged piano-stool' geometry, wherein Ru(ii) is bound to the η6-p-cymene moiety as a base and two chlorides and the amine-N of the ligand L occupies the three legs of the stool. The complexes exhibited both the possibility of covalent adduct formation via the hydrolyzed Ru-Cl bond and non-covalent intercalation binding through planar naphthalimide moieties. The complexes showed enhanced photo-cytotoxicity under low-power blue LED light irradiation (λmax = 448 nm) mediated by 1O2, thereby acting as potential PDT agents. Fluorescence microscopy studies revealed that luminescent complexes preferentially localized in both the lysosomes and nucleus for effectively targeting and damaging the nuclear DNA for PDT effects. Due to enhanced lipophilicity of [RuLCl], it showed higher internalization into MCF-7 cell, measured in terms of the ruthenium content using ICP-MS. The interaction of the complexes with human transferrin (hTf) proteins was studied through molecular docking calculations, suggesting favorable binding through histidine residues and possible internalization into cancer cells via TfR-mediated endocytosis. The luminescence properties of the complexes were well-utilized to study their cellular uptake mechanism via endocytosis using fluorescence microscopy.

Stable sub-100 nm PDMS nanoparticles as an intracellular drug delivery vehicle.

For the past few decades, polydimethylsiloxane (PDMS) elastomer has been used in plethora of biomedical applications. However, PDMS has not much been explored for intracellular drug delivery since the preparation of sub-100 nm particles, preferred for such kind of applications is extremely difficult owing to its innate nature to form a film. In this work, we have performed molecular dynamics (MD) simulation for developing a strategy to restrict the inherent film-forming tendency of PDMS for obtaining stable sub-100 nm PDMS nanoparticles. MD simulation results suggest that introduction of hydroxyl groups on the surface of PDMS improves its stability in the form of nanoparticles. Based on the MD simulation results, for the first time, sub-100 nm PDMS nanoparticles are prepared via in situ surface modification of PDMS with sodium hydroxide inside nanoemulsion droplets. The synthesized nanoparticles are 30-40 nm in size, extremely soft in nature, moderately hydrophobic and stable in phosphate buffered saline. In vitro results demonstrate the synthesized PDMS nanoparticles to possess excellent biocompatibility and an intrinsic capability of selective localization in mitochondria of cancer cells. Furthermore, efficient mitochondrial delivery of anticancer drug doxorubicin through PDMS nanoparticles advocates for their suitability as a potential candidate for developing advanced nanomedicine.

Biomimetic algal polysaccharide coated 3D nanofibrous scaffolds promote skin extracellular matrix formation.

Development of functional biological substitutes for skin tissue engineering applications has observed several advancements over the past few decades. In this regard, intelligent extracellular matrix (ECM) mimetic scaffolds have recently evolved as a promising paradigm by presenting instructive cues directing cell-matrix communication, tissue remodeling and homeostasis. However, orchestring multitude attributes of skin ECM yet presents an intriguing challenge to be addressed. In the present work, we have developed an in vitro skin scaffold by coating a bio-mimetic ECM cue κ-carrageenan on electrospun nanofibers for the first time. κ-Carrageenan, a natural sulfated algal polysaccharide exhibits close similarity with native glucosaminoglycans (GAGs) of skin ECM. On the other hand, electrospun nanofibers resemble the 3D nano-topographic architecture of ECM. In the coated form, κ-carrageenan could provide the biochemical cues necessary for cellular functions on the nanofibrous scaffold, thereby mimicking the native 3D microenvironment of skin ECM. The nano-architecture of the electrospun matrix is retained in the fabricated scaffold even after coating with κ-carrageenan. The developed biomimetic scaffold significantly supplements adhesion, growth, infiltration, survival and proliferation of fibroblasts. Furthermore, enhanced gene expression and excessive secretion of collagen proteins by fibroblasts communicate a conducive skin ECM micro-environment formation on the algal polysaccharide coated nanofibrous scaffold. Taken together, these findings present a simple yet effective strategy for the fabrication of ECM mimetic scaffold for promising skin tissue engineering applications.

Design of iso-material heterostructures of TiO2via seed mediated growth and arrested phase transitions.

Stabilization of different morphologies of iso-material native/non-native heterostructures is important for electron-hole separation in the context of photo-electrochemical and opto-electronic devices. In this regard, we explore the stabilities of different morphologies of rutile ("native", ground state phase) and anatase ("non-native" phase) TiO2 heterostructures through (1) seed-mediated growth and (2) a thermally induced arrested phase transition synthesis protocol. Furthermore, the experimental results are analyzed through a combination of Density Functional Tight Binding (DFTB) and Finite Element Model (FEM) methods. During the seed-mediated growth, anatase is grown over a polydispersed and polycrystalline rutile core through thermal treatment yielding core-shell, Janus and yolk-shell iso-material heterostructures as observed from HRTEM. The arrested phase transition of anatase to rutile at different annealing temperatures yields rutile crystals in the subsurface region of the anatase and rutile/core-thin anatase/shell heterostructures but does not yield a Janus structure. Small particles that can be modeled via DFTB computations suggest that: (1) a heterostructure of the rutile/core-anatase/shell is energetically more stable than the anatase/core-rutile/shell or any other Janus configuration, (2) the off-centered rutile/core-anatase shell is more favorable to the mid-centered rutile/core-anatase shell and (3) Janus heterostructures can be stabilized when the mass ratio of the rutile seed to anatase overgrowth is high. FEM simulations, performed to evaluate the importance of stress relaxation in bicrystalline materials without defects, suggest that Janus structures can be stabilized in larger particles. The present studies add to the heuristics available for synthesizing iso-material heterostructures.

NaGdF4:Yb,Er-Ag nanowire hybrid nanocomposite for multifunctional upconversion emission, optical imaging, MRI and CT imaging applications.

The effect of novel silver nanowire encapsulated NaGdF4:Yb,Er hybrid nanocomposite on the upconversion emission and bioimaging properties has been investigated. The upconvension nanomaterials were synthesised by polyol method in the presence of ethylene glycol, PVP and ethylenediamine. The NaGdF4:Yb,Er-Ag hybrid was formed with upconverting NaGdF4:Yb,Er nanoparticles of size ~ 80 nm and silver nanowires of thickness ~ 30 nm. The surface plasmon induced by the silver ion in the NaGdF4:Yb,Er-Ag nanocomposite resulted an intense upconversion green emission at 520 nm and red emission at 660 nm by NIR diode laser excitation at 980 nm wavelength. The UV-Vis-NIR spectral absorption at 440 nm and 980 nm, the intense Raman vibrational modes and the strong upconversion emission results altogether confirm the localised surface plasmon resonance effect of silver ion in the hybrid nanocomposite. MRI study of both NaGdF4:Yb,Er nanoparticle and NaGdF4:Yb,Er-Ag nanocomposite revealed the T1 relaxivities of 22.13 and 10.39 mM-1 s-1, which are larger than the commercial Gd-DOTA contrast agent of 3.08 mM-1 s-1. CT imaging NaGdF4:Yb,Er-Ag and NaGdF4:Yb,Er respectively showed the values of 53.29 HU L/g and 39.51 HU L/g, which are higher than 25.78 HU L/g of the CT contrast agent Iobitridol. The NaGdF4:Yb,Er and NaGdF4:Yb,Er-Ag respectively demonstrated a negative zeta potential of 54 mV and 55 mV, that could be useful for biological application. The in vitro cytotoxicity of the NaGdF4:Yb,Er tested in HeLa and MCF-7 cancer cell line by MTT assay demonstrated a cell viability of 90 and 80 %, respectively. But, the cell viability of NaGdF4:Yb,Er-Ag slightly decreased to 80 and 78%. The confocal microscopy imaging showed that the UCNPs are effectively up-taken inside the nucleolus of the cancer cells, and it might be useful for NIR laser-assisted phototherapy for cancer treatment. Graphical abstract.