Therapeutic potential of 18-ß-glycyrrhetinic acid-loaded poly (lactic-co-glycolic acid) nanoparticles on cigarette smoke-induced in-vitro model of COPD.

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-ß-glycyrrhetinic acid (18ßGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18ßGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated ß galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18ßGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18ßGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings.

Direct measurement of self-diffusiophoretic force generated by active colloids of different patch coverage using optical tweezers.

HYPOTHESIS: Synthetic micro/nanomotors are gaining extensive attention for various biomedical applications (especially in drug delivery) due to their ability to mimic the motion of biological micro/nanoscale swimmers. The feasibility of these applications relies on tight control of propulsion speed, direction, and type of motion (translation, circular, etc.) along with the exerted self-propulsive force. We propose to exploit the variation of both self-propulsion speed and force of active colloids with different patch coverages (with and without supporting layer) for engineering diffusiophoretic micro/nanomotors. EXPERIMENTS: The microswimmers were designed at various patch coverages (10°, 30°, and 90°) with (Ti/Pt) and without (Pt) an adhesion layer for the catalytic patch through glancing angle metal deposition (GLAD) technique. Mean-square displacement (MSD) analysis was performed to obtain the self-propulsion parameters like speed and angular speed. Using optical tweezers (OT), the self-propulsive force was measured from the force power spectral density. FINDINGS: The findings of our experiments suggest the non-requirement of any adhesion layer preceding the catalyst deposition since the Pt 10° colloidal batch had the maximal self-propulsion speed (4.61±0.3µm/s) and force (345±57fN) for 5% w/v H2O2 fuel concentration. Moreover, the self-propulsion speed and force decreased with increasing patch size, contrary to theoretical estimates. Also, the self-propulsive force obtained from MSD is 2 to 4 times lower in magnitude than the OT based force values. We believe that the self-propelling motion of the micromotors is possibly hindered due to interactions with the surface of the quartz cuvette during the optical microscopic analysis. Further, the MSD is limited to the self-propulsive motion in two dimensions. On the other hand, OT based force measurement involve trapping the particles in the bulk of the solution entirely avoiding the particle-substrate interactions. Hence, OT based force measurements are better than the propulsion velocity based stokes drag force estimates. We believe that this study can lay the foundation in designing efficient micro/nanomotors for translational biomedical applications.

A review of the physiological effects of microgravity and innovative formulation for space travelers.

During the space travel mission, astronauts' physiological and psychological behavior will alter, and they will start consuming terrestrial drug products. However, factors such as microgravity, radiation exposure, temperature, humidity, strong vibrations, space debris, and other issues encountered, the drug product undergo instability This instability combined with physiological changes will affect the shelf life and diminish the pharmacokinetic and pharmacodynamic profile of the drug product. Consequently, the physicochemical changes will produce a toxic degradation product and a lesser potency dosage form which may result in reduced or no therapeutic action, so the astronaut consumes an additional dose to remain healthy. On long-duration missions like Mars, the drug product cannot be replaced, and the astronaut may relay on the available medications. Sometimes, radiation-induced impurities in the drug product will cause severe problems for the astronaut. So, this review article highlights the current state of various space-related factors affecting the drug product and provides a comprehensive summary of the physiological changes which primarly focus on absorption, distribution, metabolism, and excretion (ADME). Along with that, we insist some of the strategies like novel formulations, space medicine manufacturing from plants, and 3D printed medicine for astronauts in longer-duration missions. Such developments are anticipated to significantly contribute to new developments with applications in both human space exploration and on terrestrial healthcare.

Development of Hematite Nano Ellipsoids/Pectin Composite Films for Green Packaging Applications.

Synthetic packaging materials are known to cause serious environmental and human health problems. Among the eco-friendly biopolymers from nonfood sources that are suitable for packaging applications, pectin is a promising candidate. However, native pectin films (NPF) exhibit poor mechanical strength, high hydrophilicity, and poor gas diffusion barrier properties. These shortcomings offset the advantages of pectin as a potential packaging material. To address these limitations, in this study, hematite nano ellipsoids (HNEs) were incorporated as fillers to reinforce native pectin films. This reinforcement resulted in substantial improvements in the mechanical properties, hydrophobicity, thermal stability, barrier properties, and optical attributes of pectin films. Compared to NPF, the pectin-hematite composite film exhibited a 35% increase in tensile strength, a 30° increase in contact angle, a 6-fold increase in the oxygen diffusion barrier properties, and a 20% increase in the water vapor barrier properties. This study presents a sustainable, biocompatible, and biodegradable packaging solution by capitalizing on eco-friendly biopolymer and nanoparticle engineering.

Drying-Induced Flash Nanoprecipitation in a Sessile Drop: A Route to Synthesize Polymeric Nanoparticles.

Flash nanoprecipitation is a simple and scalable method to produce nanoparticles by rapid mixing of a polymer solution with an antisolvent. High-speed mixing devices for the continuous synthesis of polymeric nanoparticles and drug-encapsulated nanoparticles have been designed. In this work, we demonstrate a different approach to induce flash nanoprecipitation using the differential evaporation of solvents in a sessile drop. To show proof of concept, we use polymethyl-methacrylate (PMMA) dissolved in a tetrahydrofuran (THF)-water mixture as a model system. A sessile drop of the polymer solution is allowed to dry under controlled conditions. The sessile drops of the PMMA-THF-water ternary mixture are observed to dry in the constant radius mode. As THF in the drop evaporates faster than water, PMMA supersaturates and precipitates as nanoparticles. Although coffee-ring formation is well-studied in the drying of colloidal suspensions, this work demonstrates the formation of nanoparticles in situ due to a change of solvent quality and subsequent deposition of particles at the pinned contact line. Using the theory of drying of binary solutions, we calculate the temporal variation of composition. The drying paths passing through the low-concentration branch of the binodal give rise to nanoparticles, whereas those passing through the high-concentration branch yield porous films. Spherical polymeric nanoparticles in the size range of 250-700 nm were synthesized using this technique starting from drops with different initial polymer concentration. The method is a cost-effective (no high-speed mixing is required) and scalable alternative to conventional flash nanoprecipitation for synthesizing polymeric nanoparticles for potential applications in drug delivery, diagnostics, and polymer recycling.

Doxorubicin loaded thermostable nanoarchaeosomes: a next-generation drug carrier for breast cancer therapeutics.

Breast cancer has a poor prognosis due to the toxic side effects associated with high doses of chemotherapy. Liposomal drug encapsulation has resulted in clinical success in enhancing chemotherapy tolerability. However, the formulation faces severe limitations with a lack of colloidal stability, reduced drug efficiency, and difficulties in storage conditions. Nanoarchaeosomes (NA) are a new generation of highly stable nanovesicles composed of the natural ether lipids extracted from archaea. In our study, we synthesized and characterized the NA, evaluated their colloidal stability, drug release potential, and anticancer efficacy. Transmission electron microscopy images have shown that the NA prepared from the hyperthermophilic archaeon Aeropyrum pernix K1 was in the size range of 61 ± 3 nm. The dynamic light scattering result has confirmed that the NA were stable at acidic pH (pH 4) and high temperature (70 °C). The NA exhibited excellent colloidal stability for 50 days with storage conditions at room temperature. The cell viability results have shown that the pure NA did not induce cytotoxicity in NIH 3T3 fibroblast cells and are biocompatible. Then NA were loaded with doxorubicin (NAD), and FTIR and UV-vis spectroscopy results have confirmed high drug loading efficiency of 97 ± 1% with sustained drug release for 48 h. The in vitro cytotoxicity studies in MCF-7 breast cancer cell lines showed that NAD induced cytotoxicity at less than 10 nM concentration. Fluorescence-activated cell sorting (FACS) results confirmed that NAD induced late apoptosis in nearly 92% of MCF-7 cells and necrosis in the remaining cells with cell cycle arrest at the G0/G1 phase. Our results confirmed that the NA could be a potential next-generation carrier with excellent stability, high drug loading efficiency, sustained drug release ability, and increased therapeutic efficacy, thus reducing the side effects of conventional drugs.

18-ß-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro.

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-ß-glycyrrhetinic acid (18-ß-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-ß-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1ß), mimicking what happens in smokers and COPD patients. Treatment with 18-ß-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1ß levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-ß-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.

Elucidating shape-mediated drug carrier mechanics of hematite nanomaterials for breast cancer therapeutics.

Metallic nanomaterials have gained significant attention in cancer therapy as potential nanocarriers due to their unique properties at the nanoscale. However, nanomaterials face several drawbacks, including biocompatibility, stability, and cellular uptake. Hematite (α-Fe2O3) nanoparticles are emerging as promising nano-carriers to reduce adverse outcomes of conventional chemotherapeutics. However, the shape-mediated drug carrier mechanics of hematite nanomaterials are not raveled. In this study, we tailored hematite nanoparticles in ellipsoidal (EHNP) and spherical (SHNP) shapes with excellent biocompatibility and efficient drug encapsulation and release. We elucidate that EHNP exhibits higher cellular uptake than SHNP. With effective cellular internalization, the cisplatin-loaded EHNP showed excellent cytotoxicity with an IC50 value of 200 nM compared to the cisplatin-loaded SHNP. The flow cytometry cell sorting (FACS) analysis showed a four-fold increase in cell death by arresting the cells at the G0/G1 and G1 phases for cis-EHNP compared to cis-SHNP. The results show that ellipsoidal-shaped hematite nanoparticles can act as attractive nanocarriers with improved therapeutic efficacy in cancer therapy.

Graphene: A Multifaceted Carbon-Based Material for Bone Tissue Engineering Applications.

Tissue engineering is an emerging technological field that aims to restore and replace human tissues. A significant number of individuals require bone replacement annually as a result of skeletal abnormalities or accidents. In recent decades, notable progress has been made in the field of biomedical research, specifically in the realm of sophisticated and biocompatible materials. The purpose of these biomaterials is to facilitate bone tissue regeneration. Carbon nanomaterial-based scaffolds are particularly notable due to their accessibility, mechanical durability, and biofunctionality. The scaffolds exhibit the capacity to enhance cellular proliferation, mitigate cell damage, induce bone tissue growth, and maintain biological compatibility. Therefore, they play a crucial role in the development of the bone matrix and the necessary cellular interactions required for bone tissue restoration. The attachment, growth, and specialization of osteogenic stem cells on biomaterial scaffolds play critical roles in bone tissue engineering. The optimal biomaterial should facilitate the development of bone tissue in a manner that closely resembles that of human bone. This comprehensive review encompasses the examination of graphene oxide (GO), carbon nanotubes (CNTs), fullerenes, carbon dots (CDs), nanodiamonds, and their respective derivatives. The biomaterial frameworks possess the ability to replicate the intricate characteristics of the bone microenvironment, thereby rendering them suitable for utilization in tissue engineering endeavors.

Chitosan derived chito-oligosaccharides promote osteoblast differentiation and offer anti-osteoporotic potential: Molecular and morphological evidence from a zebrafish model.

This study delves into the potential of chito-oligosaccharides (COS) to promote osteoblast differentiation and prevent osteoporosis, utilizing experiments with mouse MSCs and the zebrafish model. The preliminary biocompatibility study affirms the non-toxic nature of COS across various concentrations. In the osteoblast differentiation study, COS enhances ALP activity and calcium deposition at the cellular level. Moreover, COS induces the upregulation of molecular markers, including Runx2, Type I collagen, ALP, osteocalcin, and osteonectin in mouse MSCs. Zebrafish studies further demonstrate COS's anti-osteoporotic effects, showcasing its ability to expedite fin fracture repair, vertebral mineralization, and bone mineralization in dexamethasone-induced osteoporosis models. The scale regenerative study reveals that COS mitigates the detrimental effects of dexamethasone induced osteoclastic activity, reducing TRAP and hydroxyproline levels while elevating the expression of Runx2a MASNA isoform, collagen2α, OC, and ON mRNAs. Additionally, COS enhances calcium and phosphorus levels in regenerated scales, impacting the bone-healthy calcium-to­phosphorus ratio. The study also suggests that COS modulates the MMP3-Osteopontin-MAPK signaling pathway. Overall, this comprehensive investigation underscores the potential of COS to prevent and treat osteoporosis. Its multifaceted cellular and molecular effects, combined with in vivo bone regeneration and repair, propose that COS may be effective in addressing osteoporosis and related bone disorders. Nonetheless, further research is imperative to unravel underlying mechanisms and optimize clinical applications.

Liquid-Liquid Phase Separation (LLPS)-Driven Fibrilization of Amyloid-ß Protein.

Amyloid-ß [Aß(1-40)] aggregation into a fibrillar network is one of the major hallmarks of Alzheimer's disease (AD). Recently, a few studies reported that polyphosphate (polyP), an anionic biopolymer that participates in various cellular physiological processes in humans, induces fibrilization in many amyloidogenic proteins [ 2020 Alzheimer's Disease Facts and Figures; John Wiley and Sons Inc., 2020; Tanzi, R. E.; Bertram, L. Cell 2005, 120, 545-555; Selkoe, D. J. Proc. Natl. Acad. Sci. U.S.A. 1995, 275, 630-631; and Rambaran, R. N.; Serpell, L. C. Prion 2008, 2, 112-117]. However, the role of polyP in Aß(1-40) fibrilization and the underlying mechanism are unclear. In this study, we report experimental investigations on the role of polyP in the fibrilization kinetics of Aß(1-40). It is found that polyP exhibits a dual effect depending upon the pH value. At pH = 7 (neutral), polyP inhibits amyloid fibrilization in a dose-dependent manner similar to negatively charged nanoparticles. On the contrary, at pH = 3 (acidic), polyP accelerates amyloid fibrilization kinetics via liquid-liquid phase separation (LLPS), wherein the protein-rich droplets contain mature fibrils. In the parameter space spanned by concentrations of Aß(1-40) and polyP, a phase diagram is constructed to demark the domain where LLPS is observed at pH = 3. Characterization of the protein aggregates, secondary structure content in the aggregates, and cell viability studies in the presence of aggregates are discussed at both pH values. This study reveals that anionic biopolymers can modulate amyloid fibrilization kinetics, linked to neurodegenerative diseases, depending upon their local concentrations and pH.

Synthesis of Germanium Nanospheres as High-Precision Optical Tweezers Probes.

Force spectroscopy on single molecular machines generating piconewton forces is often performed using optical tweezers. Since trapping forces scale with the particle volume, piconewton-force measurements so far required micron-sized probes practically limiting the spatiotemporal resolution. Here, we have overcome this limit by developing high-refractive index germanium nanospheres as ultraresolution trapping probes. With a refractive index of 4.4, their trapping efficiency and maximum force per power is more than 10-fold higher compared to silica spheres of equal size. Therefore, the use of germanium allows piconewton-force measurements with nanometer sized probes. Using 70-nm-diameter germanium nanospheres as trappable optical probes (GeNTOPs), we could show that kinesin-1 walks with 4-nm-center-of-mass steps. In the long-term, the application of these novel high-precision GeNTOPs will provide new insight into the working mechanism of molecular machines and are promising candidates for other applications in microscopy, optoelectronics, and nanophotonics.

Kinetics of aggregation of amyloid ß under different shearing conditions: Experimental and modelling analyses.

Amyloid ß (Aß40) is a class of amyloidogenic proteins known to aggregate into a fibrillar network. The rate of aggregation and fibril yield is sensitive to external energy input, such as shear. In this work, simple shear and shaking experiments are performed on Aß40 solution using a Couette cell and an orbital shaker, respectively. Experiments show that, under uniform shear, both the mass of fibrils and aggregation rate increase with the shear rate. In the case of orbital shaking, the lag time decreases with the rotational speed of the shaker, but the final fibril mass is the same for all agitation speeds. To explain this contrasting behavior of aggregation kinetics, a population balance model is developed to account for the effect of shear on the aggregation of Aß. The kinetic model includes primary nucleation, secondary nucleation, elongation, fragmentation, and depolymerization steps. The effect of steady uniform shear is encoded in the depolymerization rate constant (kd), and it is shown that kd decreases with shear rate initially and saturates at high shear rates. A competition between elongation and depolymerization rates yields different equilibrium masses of fibril at different shear rates. The model results agree quantitatively well with experimental data on the rate of aggregation and mass of fibrils as a function of shear rate. The modeling framework can be used to explain the shear rate-dependent aggregation of other amyloidogenic proteins.

Anisotropic and Amphiphilic Mesoporous Core-Shell Silica Microparticles Provide Chemically Selective Environments for Simultaneous Delivery of Curcumin and Quercetin.

Porous silica materials are often used for drug delivery. However, systems for simultaneous delivery of multiple drugs are scarce. Here we show that anisotropic and amphiphilic dumbbell core-shell silica microparticles with chemically selective environments can entrap and release two drugs simultaneously. The dumbbells consist of a large dense lobe and a smaller hollow hemisphere. Electron microscopy images show that the shells of both parts have mesoporous channels. In a simple etching process, the properly adjusted stirring speed and the application of ammonium fluoride as etching agent determine the shape and the surface anisotropy of the particles. The surface of the dense lobe and the small hemisphere differ in their zeta potentials consistent with differences in dye and drug entrapment. Confocal Raman microscopy and spectroscopy show that the two polyphenols curcumin (Cur) and quercetin (QT) accumulate in different compartments of the particles. The overall drug entrapment efficiency of Cur plus QT is high for the amphiphilic particles but differs widely between Cur and QT compared to controls of core-shell silica microspheres and uniformly charged dumbbell microparticles. Furthermore, Cur and QT loaded microparticles show different cancer cell inhibitory activities. The highest activity is detected for the dual drug loaded amphiphilic microparticles in comparison to the controls. In the long term, amphiphilic particles may open up new strategies for drug delivery.

Single depolymerizing and transport kinesins stabilize microtubule ends.

Microtubules are highly dynamic cellular filaments and an accurate control of their length is important for many intracellular processes like cell division. Among other factors, microtubule length is actively modulated by motors from the kinesin superfamily. For example, yeast kinesin-8, Kip3, motors depolymerize microtubules by a cooperative, force- and length-dependent mechanism. However, whether single motors can also depolymerize microtubules is unclear. Here, we measured how single kinesin motors influenced the stability of microtubules in an in vitro assay. Using label-free interference reflection microscopy, we determined the spontaneous microtubule depolymerization rate of stabilized microtubules in the presence of kinesins. Surprisingly, we found that both single Kip3 and nondepolymerizing kinesin-1 transport motors, used as a control, stabilized microtubules further. For Kip3, this behavior is contrary to the collective force-dependent depolymerization activity of multiple motors. Because of the control measurement, the finding may hint at a more general stabilization mechanism. The complex, concentration-dependent interaction with microtubule ends provides new insights into the molecular mechanism of kinesin-8 and its regulatory function of microtubule length.

Germanium nanospheres for ultraresolution picotensiometry of kinesin motors.

Kinesin motors are essential for the transport of cellular cargo along microtubules. How the motors step, detach, and cooperate with each other is still unclear. To dissect the molecular motion of kinesin-1, we developed germanium nanospheres as ultraresolution optical trapping probes. We found that single motors took 4-nanometer center-of-mass steps. Furthermore, kinesin-1 never detached from microtubules under hindering load conditions. Instead, it slipped on microtubules in microsecond-long, 8-nanometer steps and remained in this slip state before detaching or reengaging in directed motion. Unexpectedly, reengagement and thus rescue of directed motion was more frequent. Our observations broaden our knowledge on the mechanochemical cycle and slip state of kinesin. This state and rescue need to be accounted for to understand long-range transport by teams of motors.

Polycationic gold nanorods as multipurpose in vitro microtubule markers.

Gold nanoparticles are intriguing because of their unique size- and shape-dependent chemical, electronic and optical properties. Gold nanorods (AuNRs) are particularly promising for various sensor applications due to their tip-enhanced plasmonic fields. For biomolecule attachment, AuNRs are often functionalized with proteins. However, by their intrinsic size such molecules block the most sensitive near-field region of the AuNRs. Here, we used short cationic thiols to functionalize AuNRs. We show that the functionalization layer is thin and that these polycationic AuNRs bind in vitro to negatively charged microtubules. Furthermore, we can plasmonically stimulate light emission from single AuNRs in the absence of any fluorophores and, therefore, use them as bleach- and blinkfree microtubule markers. We expect that polycationic AuNRs may be applicable to in vivo systems and other negatively charged molecules like DNA. In the long-term, microtubule-bound AuNRs can be used as ultrasensitive single-molecule sensors for molecular machines that interact with microtubules.

Supported Solid Lipid Bilayers as a Platform for Single-Molecule Force Measurements.

Biocompatible surfaces are important for basic and applied research in life science with experiments ranging from the organismal to the single-molecule level. For the latter, examples include the translocation of kinesin motor proteins along microtubule cytoskeletal filaments or the study of DNA-protein interactions. Such experiments often employ single-molecule fluorescence or force microscopy. In particular for force measurements, a key requirement is to prevent nonspecific interactions of biomolecules and force probes with the surface, while providing specific attachments that can sustain loads. Common approaches to reduce nonspecific interactions include supported lipid bilayers or PEGylated surfaces. However, fluid lipid bilayers do not support loads and PEGylation may require harsh chemical surface treatments and have limited reproducibility. Here, we developed and applied a supported solid lipid bilayer (SSLB) as a platform for specific, load bearing attachments with minimal nonspecific interactions. Apart from single-molecule fluorescence measurements, anchoring molecules to lipids in the solid phase enabled us to perform force measurements of molecular motors and overstretch DNA. Furthermore, using a heating laser, we could switch the SSLB to its fluid state allowing for manipulation of anchoring points. The assay had little nonspecific interactions, was robust, reproducible, and time-efficient, and required less hazardous and toxic chemicals for preparation. In the long term, we expect that SSLBs can be widely employed for single-molecule fluorescence microscopy, force spectroscopy, and cellular assays in mechanobiology.

Rapid Dissolution of Amyloid ß Fibrils by Silver Nanoplates.

Plaques of amyloid beta (Aß) protein are associated with neurodegenerative diseases, and preventing their formation and dissolution of plaques are essential to the development of therapeutics. In this study, silver triangular nanoplates (AgTNPs) are shown to dissolve mature Aß fibrils because of their plasmonic photothermal property. Mature Aß fibrils treated with AgTNPs under near-infrared (NIR)-illuminated conditions are dissolved in less than 1 h, while an equal concentration of silver spherical nanoparticles took about 70 h. The concentration of the fibrils decreased from 10 to 0.3 µM upon treating the amyloid fibrils with AgTNPs under NIR. AgTNPs are also shown to prevent the formation of Aß fibrils by selective binding to the positively charged amyloidogenic sequence of the Aß monomer. The kinetics of inhibition by AgTNPs follows the predictions of the detailed kinetic model (Ramesh et al., Langmuir 2018, 34, 4004-4012). The kinetics of dissolution and inhibition are characterized by Congo red/ThT assay, transmission electronic microscopy, atomic force microscopy, and attenuated total reflectance Fourier transform-infrared spectroscopy. Cell viability studies on SH-SY5Y and BE-(2)-C cells using 3-[4,5-dimethy-lthi-azol-2-yl]-2,5-diphenyl-tetrazdium bromide and lactate dehydrogenase assay show that the viability of the cells increased from 33 to 70% on treating the cells with AgTNP-incubated Aß fibrils compared to the mature Aß fibrils. The study provides new insights to design plasmonic nanoparticle-based therapeutics to cure neurodegenerative diseases.