Biocompatible quaternary pullulan functionalized 2D MoS2 glycosheet-based non-leaching and infection-resistant coatings for indwelling medical implants.

Medical implants are frequently used in medicine and reconstructive surgery to treat various pathological and anatomical conditions. However, over time, biofilm formation on the surface of these implants can cause recurrent infections and subsequent inflammatory responses in the host, resulting in tissue damage, necrosis, and re-hospitalization. To address these implant-associated infections, the best approach is to create antimicrobial coatings. Here, we report the fabrication of a biocompatible, non-leaching, and contact-based antibacterial coating for implants using quaternary pullulan functionalized MoS2 (MCP) glycosheets. The cationic MCP glycosheets were coated on the surfaces of polydopamine-modified stainless steel and polyvinyl fluoride substrates through a simple process of electrostatic interaction. The developed coating showed excellent antibacterial activity (>99.5%) against E. coli and S. aureus that remained stable over 30 days without leaching out of the substrates and retained its antibacterial activity. MCP-coated implants did not induce any acute or sub-chronic toxicity to mammalian cells, both in vitro and in vivo. Furthermore, MCP coating prevented S. aureus colonization on stainless steel implants in a mouse model of implant-associated infection. The MCP coating developed in this study represents a simple, safe, and effective antibacterial coating for preventing implant-associated infections.

Palladium Nanocapsules for Photothermal Therapy in the Near-Infrared II Biological Window.

Recent developments in nanomaterials with programmable optical responses and their capacity to modulate the photothermal effect induced by an extrinsic source of light have elevated plasmonic photothermal therapy (PPTT) to the status of a favored treatment for a variety of malignancies. However, the low penetration depth of near-infrared-I (NIR-I) lights and the need to expose the human body to a high laser power density in PPTT have restricted its clinical translation for cancer therapy. Most nanostructures reported to date exhibit limited performance due to (i) activity only in the NIR-I region, (ii) the use of intense laser, (iii) need of large concentration of nanomaterials, or (iv) prolonged exposure times to achieve the optimal hyperthermia state for cancer phototherapy. To overcome these shortcomings in plasmonic nanomaterials, we report a bimetallic palladium nanocapsule (Pd Ncap)─with a solid gold bead as its core and a thin, perforated palladium shell─with extinction both in the NIR-I as well as the NIR-II region for PPTT applications toward cancer therapy. The Pd Ncap demonstrated exceptional photothermal stability with a photothermal conversion efficiency of ∼49% at the NIR-II (1064 nm) wavelength region at a very low laser power density of 0.5 W/cm2. The nanocapsules were further surface-functionalized with Herceptin (Pd Ncap-Her) to target the breast cancer cell line SK-BR-3 and exploited for in vitro PPTT applications using NIR-II light. Pd Ncap-Her caused more than 98% cell death at a concentration of just 50 µg/mL and a laser power density of 0.5 W/cm2 with an output power of only 100 mW. Flow cytometric and microscopic analyses revealed that Pd Ncap-Her-induced apoptosis in the treated cancer cells during PPTT. Additionally, Pd Ncaps were found to have reactive oxygen species (ROS) scavenging ability, which can potentially reduce the damage to cells or tissues from ROS produced during PPTT. Also, Pd Ncap demonstrated excellent in vivo biocompatibility and was highly efficient in photothermally ablating tumors in mice. With a high photothermal conversion and killing efficiency at very low nanoparticle concentrations and laser power densities, the current nanostructure can operate as an effective phototherapeutic agent for the treatment of different cancers with ROS-protecting ability.

Nanobio Interface Between Proteins and 2D Nanomaterials.

Two-dimensional (2D) nanomaterials have significantly contributed to recent advances in material sciences and nanotechnology, owing to their layered structure. Despite their potential as multifunctional theranostic agents, the biomedical translation of these materials is limited due to a lack of knowledge and control over their interaction with complex biological systems. In a biological microenvironment, the high surface energy of nanomaterials leads to diverse interactions with biological moieties such as proteins, which play a crucial role in unique physiological processes. These interactions can alter the size, surface charge, shape, and interfacial composition of the nanomaterial, ultimately affecting its biological activity and identity. This review critically discusses the possible interactions between proteins and 2D nanomaterials, along with a wide spectrum of analytical techniques that can be used to study and characterize such interplay. A better understanding of these interactions would help circumvent potential risks and provide guidance toward the safer design of 2D nanomaterials as a platform technology for various biomedical applications.

Quaternary Pullulan-Functionalized 2D MoS2 Glycosheets: A Potent Bactericidal Nanoplatform for Efficient Wound Disinfection and Healing.

Rapid emergence of multidrug-resistant bacterial strains has posed a global threat to public health. Hospital-acquired infections, especially in diabetic and burn patients, severely impede the process of wound healing, thereby causing high mortality. This calls for developing a new biomaterial that synergistically destroys pathogenic strains and also helps in promoting wound healing without causing any resistance generation. A new and highly potent antibacterial agent has been developed by integrating the bactericidal and wound healing properties of MoS2 nanosheets and a recently developed quaternized polysaccharide, pullulan (CP), into a single nanoplatform for accelerated wound therapy. MoS2 nanosheets are noncovalently functionalized with quaternized pullulan to yield glycosheets (MCP) that efficiently eradicate both Gram-negative Escherichia coli (5 µg/mL) and Gram-positive Staphylococcus aureus (10 µg/mL) within a short period of 4 h, through a synergistic action of membrane damage and chemical oxidation. MoS2 nanosheets coupled with CP exert a membrane-directed bactericidal action through distinct mechanisms of "pore-forming" and "non-pore-forming" pathways, respectively, whereas oxidative stress is induced by MoS2 nanosheets alone to collectively kill the pathogens. The MCP glycosheets have good biocompatibility and are also capable of disrupting and eradicating mature biofilms. Rapid and highly efficient in vivo wound disinfection and healing occurred upon MCP treatment through the reduction of inflammation and promotion of cellular proliferation and tissue remodeling. Thus, MCP glycosheets can emerge as a safe and potential biomaterial for better wound care management.

MoS2 nanosheets effectively bind to the receptor binding domain of the SARS-CoV-2 spike protein and destabilize the spike-human ACE2 receptor interactions.

The use of nanotechnology is becoming increasingly significant as a tool that can provide a range of options for the identification, inactivation, and therapy of coronavirus disease 2019 (COVID-19). The potential of nanoparticles as an alternative therapeutic agent to inactivate SARS-CoV-2 is continually being investigated. Herein, we have explored the interaction of 2D molybdenum disulfide (MoS2) nanosheets with the SARS-CoV-2 spike protein, human ACE2 receptor and the complex formed between them through molecular docking and atomistic simulations. The results indicated that MoS2 nanosheets can effectively bind to the receptor binding domain (RBD) of the spike protein with good docking energies. It is interesting to note that this also applied to the extensively glycosylated spike protein and its variations, Kappa and Delta. A significant loss of secondary structures was observed when MoS2 nanosheets interacted with the RBD of the spike protein. The nanosheets interacted strongly with the proteins through a number of hydrogen bonds and van der Waals interactions. Moreover, the binding of the MoS2 nanosheets at different locations of the RBD or ACE2 in the spike-RBD/ACE2 complex resulted in significant conformational changes. Detailed energetics and solvent accessibility calculations revealed that, when present at the interface, MoS2 nanosheets can be a potential inhibitory agent. The findings were supported by de-wetting calculations, indicating strong adherence of the RBD of spike protein on the MoS2 nanosheet and de-stability of the spike-ACE2 interaction. Thus, the findings clearly demonstrate the antiviral potential of 2D MoS2 nanosheets, prompting its further exploration for combating COVID-19.

Antimicrobial mechanisms of biomaterials: from macro to nano.

Overcoming the global concern of antibiotic resistance is one of the biggest challenges faced by scientists today, and the key to tackling this issue of emerging infectious diseases is the development of next-generation antimicrobials. The rapid emergence of multi-drug resistant microbes, superbugs and mutated strains of viruses has fuelled the search for new and alternative antimicrobial agents with broad-spectrum biocidal activity. Biomaterials, ranging from macroscopic polymers, proteins, and peptides to nanoscale materials such as nanoparticles, nanotubes and nanosheets have emerged as effective antimicrobials. An extensive body of research has established the antibacterial and antiviral efficiencies of different types of biomaterials. What make these materials unique are the different modes through which they interact and exert their antimicrobial activity. This review provides a comprehensive and detailed overview of the diverse modes of interaction between biomaterials and bacteria and viruses, and sheds light on how different biomaterials influence and modulate antimicrobial mechanisms to achieve a high degree of therapeutic efficacy without resistance generation.

Anionic Lipid Clustering-Mediated Bactericidal Activity and Selective Toxicity of Quaternary Ammonium-Substituted Polycationic Pullulan against the Staphylococcus aureus Bacterial Membrane.

Non-amphiphilic polycations have recently been recognized to hold excellent antimicrobial potential with great mammalian cell compatibility. In a recent study, the excellent broad-spectrum bactericidal efficacy of a quaternary ammonium-substituted cationic pullulan (CP4) was demonstrated. Their selective toxicity and nominal probability to induce the acquisition of resistance among pathogens fulfill the fundamental requirements of new-generation antibacterials. However, there have been exiguous attempts in the literature to understand the antimicrobial activity of polycations against Gram-positive bacterial membranes. Here, for the first time, we have scrutinized the molecular level interactions of CP4 tetramers with a model Staphylococcus aureus membrane to understand their probable antibacterial function using molecular dynamics simulations. Our analysis reveals that the hydrophilic CP4 molecules are spontaneously adsorbed onto the membrane outer leaflet surface by virtue of strong electrostatic interactions and do not penetrate into the lipid tail hydrophobic region. This surface binding of CP4 is strengthened by the formation of anionic lipid-rich domains in their vicinity, causing lateral compositional heterogeneity. The major outcomes of the asymmetric accumulation of bulky polycationic CP4 on one leaflet are (i) anionic lipid segregation at the interaction site and (ii) a decrease in the cationic lipid acyl tail ordering and ease of water translocation across the lipid hydrophobic barrier. The membrane-CP4 interactions are strongly monitored by the ionic strength; a higher salt concentration weakens the binding of CP4 on the membrane surface. In addition, our study also substantiates the non-interacting behavior of CP4 oligomers with biomimetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane, indicating their cell selectivity and specificity against pathogenic membranes.

Nanotechnology Toolkit for Combating COVID-19 and Beyond.

The outbreak of SARS-CoV-2 is unlikely to be contained anytime soon with conventional medical technology. This beckons an urgent demand for novel and innovative interventions in clinical protocols, diagnostics, and therapeutics; to manage the current "disease X" and to be poised to counter its successor of like nature if one were to ever arise. To meet such a demand requires more attention to research on the viral-host interactions and on developing expeditious solutions, the kinds of which seem to spring from promising domains such as nanotechnology. Inducing activity at scales comparable to the viruses themselves, nanotechnology-based preventive measures, diagnostic tools and therapeutics for COVID-19 have been rapidly growing during the pandemic. This review covers the recent and promising nanomedicine-based solutions relating to COVID-19 and how some of these are possibly applicable to a wider range of viruses and pathogens. We also discuss the type, composition, and utility of nanostructures which play various roles specifically under prevention, diagnosis, and therapy. Further, we have highlighted the adoption and commercialization of some the solutions by large and small corporations alike, as well as providing herewith an exhaustive list on nanovaccines.

Nano-bio interactions of 2D molybdenum disulfide.

Two-dimensional (2D) molybdenum disulfide (MoS2) is an ultrathin nanomaterial with a high degree of anisotropy, surface-to-volume ratio, chemical functionality and mechanical strength. These properties together enable MoS2 to emerge as a potent nanomaterial for diverse biomedical applications including drug delivery, regenerative medicine, biosensing and bioelectronics. Thus, understanding the interactions of MoS2 with its biological interface becomes indispensable. These interactions, referred to as "nano-bio" interactions, play a key role in determining the biocompatibility and the pathways through which the nanomaterial influences molecular, cellular and biological function. Herein, we provide a critical overview of the nano-bio interactions of MoS2 and emphasize on how these interactions dictate its biomedical applications including intracellular trafficking, biodistribution and biodegradation. Also, a critical evaluation of the interactions of MoS2 with proteins and specific cell types such as immune cells and progenitor/stem cells is illustrated which governs the short-term and long-term compatibility of MoS2-based biomedical devices.

Superior Peroxidase-Like Activity of Gold Nanorattles in Ultrasensitive H2 O2 Sensing and Antioxidant Screening.

Nanozymes are artificial enzyme systems which are easy to produce, highly stable and cost-effective in comparison to natural enzymes. Herein, we evaluated the peroxidase-like activity of gold nanorattles (Au NRTs) having a solid gold octahedron core and thin, porous cubic gold shell. We also prepared solid gold nanocubes and nanospheres of similar sizes and surface charge as that of Au NRTs and compared their activity with standard horse radish peroxidase (HRP). All the prepared nanostructures followed Michaelis-Menten kinetics as observed from their substrate concentration vs. initial reaction velocity plot using 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate. The kinetic parameters and the catalytic efficiency for the peroxidase-like activity of the nanostructures and HRP were calculated, and it was observed that Au NRTs possess the best nanozymatic activity with lowest KM and highest catalytic efficiency (kcat /KM ). The better activity of Au NRTs compared with other nanostructures and HRP could be attributed to the hollow porous structure with a solid core where different surfaces are available for reaction. Au NRTs, being the best amongst the tested nanozymes were further used for the sensing of hydrogen peroxide (H2 O2 ) and were found to sense H2 O2 down to 0.5 µM. Further, two naturally occurring antioxidants, tannic acid and ascorbic acid showed inhibitory effect on the peroxidase-like activity of Au NRTs in a concentration dependent manner which can be further used for screening of antioxidants or for determining the antioxidant potential.

Quaternary ammonium substituted pullulan accelerates wound healing and disinfects Staphylococcus aureus infected wounds in mouse through an atypical 'non-pore forming' pathway of bacterial membrane disruption.

The emergence of multi-drug resistant pathogens has fueled the search for alternatives to the existing line of antibiotics that can eradicate pathogens without inducing resistance development. Here, we report the accelerated wound healing and disinfection potential of a non-amphiphilic quaternized fungal exopolysaccharide, pullulan, without resistance generation in pathogens. The quaternary ammonium substituted pullulan (CP) derivatives showed excellent bactericidal activity against both Gram negative (MBC90 = 1.5 µg mL-1) and Gram positive (MBC90 = 0.25 µg mL-1) bacteria at very low concentrations without showing any toxicity towards mammalian cells. A combined approach of atomistic molecular dynamics simulation and experimental assays revealed that CP exerts a membrane directed bactericidal action through an atypical "non-pore forming" pathway which is not yet established for any known antibacterial polysaccharides. This involves an increase in membrane roughness, disorder among anionic lipid tails, formation of localized anionic lipid clusters and membrane depolarization, finally leading to physical disruption of the membrane integrity. Moreover, CP also displayed biofilm eradication abilities and emerged as an excellent therapeutic material for disinfection and healing of infected wounds. The present work shows the potential of exploiting polysaccharides as next-generation broad-spectrum antimicrobials and provides a platform for further development of rationally designed pullulan-based functional materials for biomedical applications.

Reusable MoS2-Modified Antibacterial Fabrics with Photothermal Disinfection Properties for Repurposing of Personal Protective Masks.

The current pandemic caused by SARS-CoV-2 has seen a widespread use of personal protective equipment, especially face masks. This has created the need to develop better and reusable protective masks with built-in antimicrobial, self-cleaning, and aerosol filtration properties to prevent the transmission of air-borne pathogens such as the coronaviruses. Herein, molybdenum disulfide (MoS2) nanosheets are used to prepare modified polycotton fabrics having excellent antibacterial activity and photothermal properties. Upon sunlight irradiation, the nanosheet-modified fabrics rapidly increased the surface temperature to ∼77 °C, making them ideal for sunlight-mediated self-disinfection. Complete self-disinfection of the nanosheet-modified fabric was achieved within 3 min of irradiation, making the fabrics favorably reusable upon self-disinfection. The nanosheet-modified fabrics maintained the antibacterial efficiency even after 60 washing cycles. Furthermore, the particle filtration efficiency of three-layered surgical masks was found to be significantly improved through incorporation of the MoS2-modified fabric as an additional layer of protective clothing, without compromising the breathability of the masks. The repurposed surgical masks could filter out around 97% of 200 nm particles and 96% of 100 nm particles, thus making them potentially useful for preventing the spread of coronaviruses (120 nm) by trapping them along with antibacterial protection against other airborne pathogens.

DNA binding and NIR triggered DNA release from quaternary ammonium modified poly(allylamine hydrochloride) functionalized and folic acid conjugated reduced graphene oxide nanocomposites.

Reduced graphene oxide (RGO) has shown tremendous potential as a NIR responsive nanomaterial and has been extensively explored for NIR mediated photothermal therapy and drug delivery. However, the potential of NIR as a stimulus to trigger release of entrapped/complexed DNA from its surface have not been explored. Strong complexation between the loaded cargo and the carrier often leads to no-release or decrease in the release of the therapeutic cargo. Herein, we investigated NIR as a stimulus for inducing DNA release from RGO nanocomposites. A quaternary ammonium modified poly(allylamine hydrochloride) functionalized RGO nanocomposite (RGO-MPAH) was synthesized, which was further tagged with a targeting moiety, folic acid (FA). The structural, optical and chemical properties of the synthesized nanocomposites were characterized which validated successful reduction and functionalization of GO with PAH/MPAH. The nanocomposites were found to be non-toxic and showed excellent DNA binding ability at complexation ratios as low as 3:1 (w/w). Additionally, the nanocomposites demonstrated NIR responsive release of complexed DNA from their surfaces, with RGO-PAH showing maximum DNA release followed by RGO-MPAH and RGO-MPAH-FA. This study shows the potential of NIR light to act as a stimulus for inducing release of entrapped nucleic acids from the surface of nanocarriers.

Gold nanoparticle surface engineering strategies and their applications in biomedicine and diagnostics.

Gold nanoparticles (AuNPs) have found a wide range of biomedical and environmental monitoring applications (viz. drug delivery, diagnostics, biosensing, bio-imaging, theranostics, and hazardous chemical sensing) due to their excellent optoelectronic and enhanced physico-chemical properties. The modulation of these properties is done by functionalizing them with the synthesized AuNPs with polymers, surfactants, ligands, drugs, proteins, peptides, or oligonucleotides for attaining the target specificity, selectivity and sensitivity for their various applications in diagnostics, prognostics, and therapeutics. This review intends to highlight the contribution of such AuNPs in state-of-the-art ventures of diverse biomedical applications. Therefore, a brief discussion on the synthesis of AuNPs has been summarized prior to comprehensive detailing of their surface modification strategies and the applications. Here in, we have discussed various ways of AuNPs functionalization including thiol, phosphene, amine, polymer and silica mediated passivation strategies. Thereafter, the implications of these passivated AuNPs in sensing, surface-enhanced Raman spectroscopy (SERS), bioimaging, drug delivery, and theranostics have been extensively discussed with the a number of illustrations.

Poly(allylamine hydrochloride)-functionalized reduced graphene oxide for synergistic chemo-photothermal therapy.

AIM: To develop near-infrared (NIR) light-responsive reduced graphene oxide (RGO)-based nanocomposites with improved stability, biocompatibility and enhanced in vitro chemo-photothermal therapeutic efficiency. MATERIALS & METHODS: Poly(allylamine hydrochloride)-functionalized RGO-based nanocomposites (RGO-PAH) were synthesized and thoroughly characterized. In vitro biocompatibility, cellular uptake and in vitro synergistic chemo-photothermal therapeutic efficiency of drug-loaded RGO-PAH nanocomposites were evaluated along with elucidation of cell death mechanism. RESULTS: RGO-PAH nanocomposites showed excellent photothermal transduction, pH-dependent drug release, rapid internalization, high biocompatibility and highly efficient synergistic in vitro chemo-photothermal therapy via apoptosis induction through increase in intracellular reactive oxygen species (ROS) production followed by oxidative DNA damage. CONCLUSION: Excellent biocompatibility and highly efficient chemo-photothermal killing of cancer cells at a very low concentration reflects the potential of RGO-PAH as a NIR-responsive therapeutic agent for cancer therapy.

Plasmonic Gold Nanorattle Impregnated Chitosan Nanocarrier for Stimulus Responsive Theranostics.

Herein, a stimulus-responsive theranostic nanosystem comprising gold nanorattles (AuNRTs), having a solid octahedron core and thin porous cubic shell, encapsulated within chitosan nanocarriers (CS-AuNRT) has been reported. Due to the plasmonic AuNRTs, CS-AuNRT demonstrated unique features of near infrared (NIR) absorbance and accessible intrinsic electromagnetic "hot spots" arising due to coupling of inner solid core and outer porous shell. These properties enabled CS-AuNRTs to be used for NIR-responsive drug delivery, photothermal therapy, and surface enhanced Raman scattering (SERS) based bioimaging. Following loading of chemotherapeutic drug doxorubicin (DOX) within AuNRTs along with a phase changing material (PCM), application of NIR irradiation resulted in photothermal melting of the PCM and simultaneous payload release in the surrounding medium. Although being nontoxic themselves, CS-AuNRTs with or without loaded DOX could mount significant cell death in breast cancer cell line (MCF-7) in the presence of NIR light as external stimulus. The oxidative stress generated by DOX-loaded and empty CS-AuNRTs upon NIR irradiation were confirmed by flow-cytometric determination of intracellular reactive oxygen species (ROS). Further, the ROS-led induction of apoptosis in treated MCF-7 cells was established from characteristic nuclear fragmentation, morphological changes and membrane blebbing as observed through confocal fluorescence and scanning electron microscopy. Thus, with NIR responsive chemo-photothermal therapy and SERS based bioimaging, the present nanocarrier system holds potential for cancer theranostics.

Mechanistic Insight into the Antibacterial Activity of Chitosan Exfoliated MoS2 Nanosheets: Membrane Damage, Metabolic Inactivation, and Oxidative Stress.

Two-dimensional molybdenum disulfide (MoS2) based nanosheets functionalized or loaded with an antimicrobial agent have recently attracted attention as highly efficient antibacterial agent. MoS2 sheets act as the photothermal transducers in inducing bacterial cell death on impingement of NIR radiation or enabled cell inactivation by wrapping around the cells. However, the intrinsic ability of MoS2 to act as an effective antibacterial agent without the use of any external stimuli or antimicrobial agent is still not well explored. This study provides a detailed mechanism of antibacterial action of chitosan exfoliated MoS2 nanosheets (CS-MoS2) by deciphering the key events happening both at the membrane surface and inside the bacteria as a result of interaction of bacterial cells with the nanosheets. A simple, green, one-step process was employed for synthesizing stable and positively charged MoS2 nanosheets. The prepared nanosheets showed excellent bactericidal activity against both Gram-positive (MIC = 90 µg/mL, MBC = 120 µg/mL) and Gram-negative bacteria (MIC = 30 µg/mL, MBC = 60 µg/mL). Investigations into deciphering the mechanism of action revealed that the CS-MoS2 nanosheets interacted strongly with the bacterial cells through electrostatic interactions and caused rapid depolarization of the membranes through dent formations. On account of strong van der Waals and electrostatic forces occurring between the CS-MoS2 nanosheets and membrane phospholipid molecules, deepening of dents occurred, which resulted in complete membrane disruption and leakage of cytoplasmic contents. This led to inactivation of the bacterial respiratory pathway through inhibition of dehydrogenase enzymes and induced metabolic arrest in the cells. Simultaneously, disruption of the antioxidant defense system of the cells by increased levels of intracellular ROS subjected the cells to oxidative damage and added to the overall bactericidal action. The nanosheets also displayed antibiofilm properties and were found to be compatible with mammalian cells even at high concentrations.

2D MoS2 -Based Nanomaterials for Therapeutic, Bioimaging, and Biosensing Applications.

Molybdenum disulfide (MoS2 ), a typical layered 2D transition metal dichalcogenide, has received colossal interest in the past few years due to its unique structural, physicochemical, optical, and biological properties. While MoS2 is mostly applied in traditional industries such as dry lubricants, intercalation agents, and negative electrode material in lithium-ion batteries, its 2D and 0D forms have led to diverse applications in sensing, catalysis, therapy, and imaging. Herein, a systematic overview of the progress that is made in the field of MoS2 research with an emphasis on its different biomedical applications is presented. This article provides a general discussion on the basic structure and property of MoS2 and gives a detailed description of its different morphologies that are synthesized so far, namely, nanosheets, nanotubes, and quantum dots along with synthesis strategies. The biomedical applications of MoS2 -based nanocomposites are also described in detail and categorically, such as in varied therapeutic and diagnostic modalities like drug delivery, gene delivery, phototherapy, combined therapy, bioimaging, theranostics, and biosensing. Finally, a brief commentary on the current challenges and limitations being faced is provided, along with a discussion of some future perspectives for the overall improvement of MoS2 -based nanocomposites as a potential nanomedicine.

A deep learning-enabled portable imaging flow cytometer for cost-effective, high-throughput, and label-free analysis of natural water samples.

We report a deep learning-enabled field-portable and cost-effective imaging flow cytometer that automatically captures phase-contrast color images of the contents of a continuously flowing water sample at a throughput of 100 mL/h. The device is based on partially coherent lens-free holographic microscopy and acquires the diffraction patterns of flowing micro-objects inside a microfluidic channel. These holographic diffraction patterns are reconstructed in real time using a deep learning-based phase-recovery and image-reconstruction method to produce a color image of each micro-object without the use of external labeling. Motion blur is eliminated by simultaneously illuminating the sample with red, green, and blue light-emitting diodes that are pulsed. Operated by a laptop computer, this portable device measures 15.5 cm × 15 cm × 12.5 cm, weighs 1 kg, and compared to standard imaging flow cytometers, it provides extreme reductions of cost, size and weight while also providing a high volumetric throughput over a large object size range. We demonstrated the capabilities of this device by measuring ocean samples at the Los Angeles coastline and obtaining images of its micro- and nanoplankton composition. Furthermore, we measured the concentration of a potentially toxic alga (Pseudo-nitzschia) in six public beaches in Los Angeles and achieved good agreement with measurements conducted by the California Department of Public Health. The cost-effectiveness, compactness, and simplicity of this computational platform might lead to the creation of a network of imaging flow cytometers for large-scale and continuous monitoring of the ocean microbiome, including its plankton composition.

Design and development of benzoxazole derivatives with toll-like receptor 9 antagonism.

Toll-like receptor 9 (TLR9) is a major therapeutic target for numerous inflammatory disorders. Development of small molecule inhibitors for TLR9 remains largely empirical due to lack of structural understanding of potential TLR9 antagonism by small molecules and due to the unusual topology of the ligand binding surface of the receptor. To develop a structural model for rational design of small molecule TLR9 antagonists, an enhanced homology model of human TLR9 (hTLR9) was constructed. Binding mode analysis of a series of molecules having characteristic molecular geometry, flexibility and basicity was conducted based on crystal structure of the inhibitory DNA (iDNA) bound to horse and bovine TLR9. Interaction with specific amino acid residues in four leucine rich repeat (LRR) regions of TLR9 was identified to be critical for antagonism by small molecules. The biological validation of TLR9 antagonism and its correlation with probe-receptor interactions led to a reliable model that could be used for development of novel small molecules with potent TLR9 antagonism (IC50 30-100 nM) with excellent selectivity against TLR7.