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Background: Exosomes are endosome-derived nano-sized vesicles that have emerged as important mediators of intercellular communication and play significant roles in various diseases. However, their applications are rigorously restricted by the limited secretion competence of cells. Therefore, strategies to enhance the production and functions of exosomes are warranted. Studies have shown that nanomaterials can significantly enhance the effects of cells and exosomes in intercellular communication; however, how palladium nanoparticles (PdNPs) enhance exosome release in human leukemia monocytic cells (THP-1) remains unclear. Therefore, this study aimed to address the effect of PdNPs on exosome biogenesis and release in THP-1 cells., Methods: Exosomes were isolated by ultracentrifugation and ExoQuick TM and characterized by dynamic light scattering, nanoparticle tracking analysis system, scanning electron microscopy, transmission electron microscopy, EXOCET TM assay, and fluorescence polarization. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay., Results: PdNP treatment enhanced the biogenesis and release of exosomes by inducing oxidative stress, endoplasmic reticulum stress, apoptosis, and immunomodulation. The exosomes were spherical in shape and had an average diameter of 50-80 nm. Exosome production was confirmed via total protein concentration, exosome counts, acetylcholinesterase activity, and neutral sphingomyelinase activity. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in PdNP-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from PdNP-treated THP-1 cells than in those isolated from control cells. THP-1 cells pre-treated with N-acetylcysteine or GW4869 showed significant decreases in PdNP-induced exosome biogenesis and release., Conclusion: To our knowledge, this is the first study showing that PdNPs stimulate exosome biogenesis and release and simultaneously increase the levels of cytokines and chemokines by modulating various physiological processes. Our findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications., Competing Interests: The authors declare no conflicts of interest., (© 2021 Gurunathan et al.)

The thermoplasmonic properties of platinum nanoparticles (PtNPs) render them desirable for use in diagnosis, detection, therapy, and surgery. However, their toxicological effects and impact at the molecular level remain obscure. Nanotoxicology is mainly focused on the interactions of nanostructures with biological systems, particularly with an emphasis on elucidating the relationship between the physical and chemical properties such as size and shape. Therefore, we hypothesized whether these unique anisotropic nanoparticles could induce cytotoxicity similar to that of spherical nanoparticles and the mechanism involved. Thus, we synthesized unique and distinct anisotropic PtNPs using lycopene as a biological template and investigated their biological activities in model human acute monocytic leukemia (THP-1) macrophages. Exposure to PtNPs for 24 h dose-dependently decreased cell viability and proliferation. Levels of the cytotoxic markers lactate dehydrogenase and intracellular protease significantly and dose-dependently increased with PtNP concentration. Furthermore, cells incubated with PtNPs dose-dependently produced oxidative stress markers including reactive oxygen species (ROS), malondialdehyde, nitric oxide, and carbonylated protein. An imbalance in pro-oxidants and antioxidants was confirmed by significant decreases in reduced glutathione, thioredoxin, superoxide dismutase, and catalase levels against oxidative stress. The cell death mechanism was confirmed by mitochondrial dysfunction and decreased ATP levels, mitochondrial copy numbers, and PGC-1α expression. To further substantiate the mechanism of cell death mediated by endoplasmic reticulum stress (ERS), we determined the expression of the inositol-requiring enzyme (IRE1), (PKR-like ER kinase) PERK, activating transcription factor 6 (ATF6), and activating transcription factor 4 ATF4, the apoptotic markers p53, Bax, and caspase 3, and the anti-apoptotic marker Bcl-2. PtNPs could activate ERS and apoptosis mediated by mitochondria. A proinflammatory response to PtNPs was confirmed by significant upregulation of interleukin-1-beta (IL-1β), interferon γ (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL-6). Transcriptomic and molecular pathway analyses of THP-1 cells incubated with the half maximal inhibitory concentration (IC 50) of PtNPs revealed the altered expression of genes involved in protein misfolding, mitochondrial function, protein synthesis, inflammatory responses, and transcription regulation. We applied transcriptomic analyses to investigate anisotropic PtNP-induced toxicity for further mechanistic studies. Isotropic nanoparticles are specifically used to inhibit non-specific cellular uptake, leading to enhanced in vivo bio-distribution and increased targeting capabilities due to the higher radius of curvature. These characteristics of anisotropic nanoparticles could enable the technology as an attractive platform for nanomedicine in biomedical applications., Competing Interests: The authors declare no conflicts of interest.

Combinations of natural bee wax flavones chrysin with a chemo drug have been exhibiting high potential with reduced adverse effect. To extend the synergistic effect of chrysin and improve the MLNPs (Multi Layer Nanoparticles) performance in drug release, layer-by-layer of poly [di(sodium carboxyphenoxy)phosphazene] (PDCPP) and poly (diallyldimethyl ammonium chloride) (PDADMAC) deposited on the CaCO 3 nanoparticles (CCNPs) surface. The results suggest spherical MLNPs of 237 nm are formed with high drug loading content with enhanced cellular uptake. Under acidic conditions, multi layer structure effectively controls burst release, providing sustained drug release for long period. The combined effect of chrysin and cisplatin improved the cytotoxic potential of MLNPs at 25 μg.mL -1 concentration. Angiogenesis inhibitor chrysin activates reactive oxygen species (ROS) production and eventually leads to mitochondrial dysfunction. Furthermore, significant decreases of buccal pouch carcinoma in hamster model. Dual drug loaded MLNPs achieves 92% regressions of tumor volume as compared to cisplatin alone loaded MLNPs. In addition, Histopathology studies demonstrated the biocompatible effect of MLNPs on vital organs. This work provides a simple method to formulate multiple drugs in single nanosystem with high therapeutic efficacy on oral cancer., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Highlights: [•] Gold nanoparticles (AuNPs) have been synthesized using Podophyllum hexandrum L. [•] AuNPs induces the oxidative stress to cell death in human cervical carcinoma cells. [•] It activates the caspase-cascade to cellular death. [•] It is actively blocks G2/M phase of cell cycle. [ABSTRACT FROM AUTHOR]