Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures

To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn’t alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (dsilica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.

Where in the world are condensed counterions?

A scaling model of the concentration profiles of both condensed and free counterions is presented for solutions of spherical and cylindrical charged nanoparticles of different charge valences, nanoparticle sizes, and...

Rapid formation methods of arrays of randomly distributed Au and Ag nanoparticles, their morphologies and optical characteristics

By the method of rapid radiation heating (at a speed of 20-25 K/s) of Au and Ag films with a thickness of 4-35 nm to temperatures of 573-693 K in air and in the process of vacuum deposition of silver on heated (up to 700 K at a heating rate of 10 K/s ) glass substrates formed Au and Ag NPs arrays with nanoparticle sizes from several tens to hundreds of nanometers, the position λSPR of which is in the range of 520-597 nm for Au NPs and 424-509 nm for Ag NPs. It is established that the average size of nanoparticles depends on the thickness of gold and silver films and the annealing temperature. The results testify that glass substrates with arrays of randomly distributed gold NPs can be used as effective SERS-substrates for the investigation of Raman spectra of nanosized (50-100 nm) chalcogenide films.

Laser sintering of oxidized copper nanoparticles deposited by dry aerosol printing

Sintering of oxidized copper nanoparticles arrays in the form of lines by the local treatment of laser radiation with wavelengths of 527 nm and 980 nm was studied. To form lines with a width equal to 40–150 μm and a thickness equal to 0.5–4 μm focused aerosol jets with average nanoparticle sizes of 110 and 65 nm were used. The production of semiconductor arrays from oxidized copper nanoparticles with a specific electrical resistance of 2⋅10−3 Ω⋅m using laser radiation with a wavelength of 980 nm was demonstrated.

Using Parallel Coordinates in Optimization of Nano-Particle Drug Delivery

Nanoparticle drug delivery better targets neoplastic lesions than free drugs and thus has emerged as safer form of cancer therapy. Nanoparticle design variables are important determinants of efficacy as they influence the drug biodistribution and pharmacokinetics. Previously, we determined optimal designs through mechanistic modeling and optimization. However, the numerical nature of the tumor model and numerous candidate nanoparticle designs hinder hypothesis generation and treatment personalization. In this paper, we utilize the parallel coordinates technique to visualize high-dimensional optimal solutions and extract correlations between nanoparticle design and treatment outcomes. We found that at optimality, two major design variables are dependent, and thus the optimization problem can be reduced. In addition, we obtained an analytical relationship between optimal nanoparticle sizes and optimal distribution, which could facilitate the utilization of tumors models in preclincal studies. Our approach has simplified the results of the previously integrated modeling and optimization framework developed for nanotherapy and enhanced the interpretation and utilization of findings. Integrated mathematical frameworks are increasing in the medical field, and our method can be applied outside nanotherapy to facilitate clinical translation of computational methods.

Characterization and Biological Evaluation of Solid Dispersed Nanoparticles of Synthetic Epoksilignan Targeting Pancreatic Cancer Cell as an Anticancer Agent

MMEO (3′-methoxy-3′,4″(methylenedioxy)-2,5-epoksilignan-4′ol-6-on) is a derivative of DMEO (3′-methoxy-3″,4″(methylenedioxy)-2,5-epoksilignan-4′,6-diol) synthesized through demethylation using dimethylsulfoxide-acetic anhydride reagent. MMEO inhibits Hedgehog signaling at a concentration of 4.1 μM. The current study aimed to formulate MMEO as solid dispersed nanoparticles and determine their physicochemical properties and inhibitory activities. XRD (X-ray diffraction) analysis showed that the crystalline particles of the pure compound MMEO was smaller than MMEO nanoparticles. Image J software showed that at concentrations of 25 mg/mL and 50 mg/mL, the average nanoparticle sizes were 852.26 nm and 178.65 nm, respectively. Therefore, the MMEO solid dispersion system with the PEG 4000 polymer increases the solubility of MMEO. The higher the concentration of PEG 4000 the greater the solubility of MMEO. Treating pancreatic cancer cell lines with MMEO silenced the smoothened function by downregulating mRNA Ptch expression. This study suggests that MMEO may inhibit pancreatic cancer disease.

Continuous Microfluidic Production of Citrem-Phosphatidylcholine Nano-Self-Assemblies for Thymoquinone Delivery

Lamellar and non-lamellar liquid crystalline nanodispersions, including liposomes, cubosomes, and hexosomes are attractive platforms for drug delivery, bio-imaging, and related pharmaceutical applications. As compared to liposomes, there is a modest number of reports on the continuous production of cubosomes and hexosomes. Using a binary lipid mixture of citrem and soy phosphatidylcholine (SPC), we describe the continuous production of nanocarriers for delivering thymoquinone (TQ, a substance with various therapeutic potentials) by employing a commercial microfluidic hydrodynamic flow-focusing chip. In this study, nanoparticle tracking analysis (NTA) and synchrotron small-angle X-ray scattering (SAXS) were employed to characterize TQ-free and TQ-loaded citrem/SPC nanodispersions. Microfluidic synthesis led to formation of TQ-free and TQ-loaded nanoparticles with mean sizes around 115 and 124 nm, and NTA findings indicated comparable nanoparticle size distributions in these nanodispersions. Despite the attractiveness of the microfluidic chip for continuous production of citrem/SPC nano-self-assemblies, it was not efficient as comparable mean nanoparticle sizes were obtained on employing a batch (discontinuous) method based on low-energy emulsification method. SAXS results indicated the formation of a biphasic feature of swollen lamellar (Lα) phase in coexistence with an inverse bicontinuous cubic Pn3m phase in all continuously produced TQ-free and TQ-loaded nanodispersions. Further, a set of SAXS experiments were conducted on samples prepared using the batch method for gaining further insight into the effects of ethanol and TQ concentration on the structural features of citrem/SPC nano-self-assemblies. We discuss these effects and comment on the need to introduce efficient microfluidic platforms for producing nanocarriers for delivering TQ and other therapeutic agents.