Theranostic lyotropic liquid crystalline nanostructures for selective breast cancer imaging and therapy.

Herein, we report the development of theranostic lyotropic liquid crystalline nanostructures (LCN's) loaded with unique MnO nanoparticles (MNPs) for selective cancer imaging and therapy. MNPs serves as a fluorescent agent as well as a source of manganese (Mn2+) and enables localized oxidative stress under the hallmarks of cancer (acidosis, high H2O2 level). In pursuit of synergistic amplification of Mn2+ antitumor activity, betulinic acid (BA) is loaded in LCN's. In this investigation, nano-architecture of LCN's phase interface is established via SAXS, Cryo-TEM and Cryo-FESEM. Intriguing in vitro studies showed that the LCN's triggered hydroxyl radical production and exhibited greater selective cytotoxicity in cancer cells, ensuring the safety of normal cells. Significant tumor ablation is realized by the 96.5 % of tumor growth inhibition index of LCN's as compared to control group. Key insights into on-site drug release, local anti-cancer response, and tumor location are gained through precise guidance of fluorescent MNPs. In addition, comprehensive assessment of the safety, pharmacokinetics and tumor distribution behavior of LCN's is performed in vivo or ex vivo. This work emphasizes the promise of modulating tumor microenvironment with smart endogenous stimuli sensitive nano systems to achieve advanced comprehensive cancer nano-theranostics without any external stimulus. STATEMENT OF SIGNIFICANCE: Effective diagnosis and treatment approaches with maximum anti-cancer activity and minimal side-effects are critical to ameliorate cancer therapy. Compared to radiation, photodynamic and photothermal therapy, the specific and selective activation of tumor microenvironmental endogenous stimuli for the logical generation of cytotoxic OH· free radicals serves as an efficient therapeutic strategy for chemodynamic-cancer treatment. In this investigation, MnO nanoparticles fulfill two needs (fluorescence-based optical imaging and a source of Mn2+ based chemodynamic therapy) in one unit. This approach also ensures the safety of normal cells, as the toxic OH· free radical activity is substantially suppressed under the mild alkaline/H2O2 conditions in normal cell microenvironment.

Interfacial separation of concentrated dye mixtures from solution with environmentally compatible nitrogenous-silane nanoparticles modified with Helianthus annuus husk extract.

The capacity of an adsorbent to bind and remove dye from solution greatly depends on the type of functionalization present on the nanoparticles surface, and its interaction with the dye molecules. Within this study, nitrogenous silane nanoparticles were hydrothermally synthesized resulting in the formation of rapid and highly efficient adsorbents for concentrated mixed dyes. The amorphous silane nanoparticles exhibited a monolayer based mechanism of mixed dye adsorption with removal capacities between 416.67 and 714.29 mg/g of adsorbent. Dye removal was predominantly due to the electrostatic attraction between the positively charged silane nanoparticles (13.22-8.20 mV) and the negatively charged dye molecules (-54.23 mV). Addition of H. annuus extract during synthesis resulted in three times the surface area and 10 times increased pore volume compared to the positive control. XPS analysis showed that silane treatments had various nitrogen containing functionalities at their surface responsible for binding dye. The weak colloidal stability of silane particles (13.22-8.20 mV) was disrupted following dye binding, resulting in their rapid coagulation and flocculation which facilitated the separation of bound dye molecules from solution. The suitability for environmental applications using these treatments was supported by a bacterial viability assay showing >90% cell viability in treated dye supernatants.

Functionalization of Elongated Tetrahexahedral Au Nanoparticles and Their Antimicrobial Activity Assay.

Gold nanoparticles are inert for the human body, and therefore, they have been functionalized to provide them with antibacterial properties. Here, elongated tetrahexahedral (ETHH) Au nanoparticles were synthesized, characterized, and functionalized with lipoic acid (LA), a natural antioxidant with a terminal carboxylic acid and a dithiolane ring, to generate ETHH-LA Au nanoparticles. The antioxidant activity of Au nanoparticles was investigated in vitro, showing that LA enhances the 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging and Fe3+ ion reducing activity of ETHH-LA at higher amounts. The antimicrobial propensities of the nanoparticles were investigated against Gram-positive ( Bacillus subtilis) and Gram-negative ( Escherichia coli) bacteria through propidium iodide assay as well as disk diffusion assay. ETHH-LA Au nanoparticles showed significantly higher antimicrobial activity against B. subtilis compared with E. coli. Furthermore, ETHH-LA Au nanoparticles also showed significantly better antimicrobial activity against both bacterial strains when compared with ETHH. ETHH Au nanoparticles also bring about the oxidation of bacterial cell membrane fatty acids and produce lipid peroxides. ETHH-LA showed higher lipid peroxidation potential than that of ETHH against both bacteria tested. The hemolytic potential of Au nanoparticles was investigated using human red blood cells and ETHH-LA showed reduced hemolytic activity than that of ETHH. The cytotoxicity of Au nanoparticles was investigated using human cervical cancer cells, HeLa, and ETHH-LA Au nanoparticles showed reduced cytotoxicity than that of ETHH. Taken together, LA enhances the antimicrobial activity of ETHH Au nanoparticles and Au nanoparticles interact with the bacteria through electrostatic interactions as well as hydrophobic interactions and damage the bacterial cell wall followed by oxidation of cell membrane fatty acids.

Phytofabrication of Iron Nanoparticles for Hexavalent Chromium Remediation.

Hexavalent chromium is a genotoxic and carcinogenic byproduct of a number of industrial processes, which is discharged into the environment in excessive and toxic concentrations worldwide. In this paper, the synthesis of green iron oxide nanoparticles using extracts of four novel plant species [Pittosporum undulatum, Melia azedarach, Schinus molle, and Syzygium paniculatum (var. australe)] using a "bottom-up approach" has been implemented for hexavalent chromium remediation. Nanoparticle characterizations show that different plant extracts lead to the formation of nanoparticles with different sizes, agglomeration tendencies, and shapes but similar amorphous nature and elemental makeup. Hexavalent chromium removal is linked with the particle size and monodispersity. Nanoparticles with sizes between 5 and 15 nm from M. azedarach and P. undulatum showed enhanced chromium removal capacities (84.1-96.2%, respectively) when compared to the agglomerated particles of S. molle and S. paniculatum with sizes between 30 and 100 nm (43.7-58.7%, respectively) in over 9 h. This study has shown that the reduction of iron salts with plant extracts is unlikely to generate vast quantities of stable zero valent iron nanoparticles but rather favor the formation of iron oxide nanoparticles. In addition, plant extracts with higher antioxidant concentrations may not produce nanoparticles with morphologies optimal for pollutant remediation.

Inhibiting Bacterial Drug Efflux Pumps via Phyto-Therapeutics to Combat Threatening Antimicrobial Resistance.

Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the drug-resistant strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of in silico tools, major success stories, challenges and future prospects are also discussed.

P-gp modulatory acetyl-11-keto-ß-boswellic acid based nanoemulsified carrier system for augmented oral chemotherapy of docetaxel.

In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery. The nanoemulsion possessing desirable particle size (122±12nm), polydispersity (0.086±0.007) and zeta potential (-29.8±2.1mV) was stable against all type of physical stresses and simulated physiological conditions tested. The formulation showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly (P<0.05). In MDA-MB-231 cells, it showed less IC50, arrested cells in G2-M phase and exhibited higher degree of apoptosis than marketed formulation Taxotere®. The 182.58±4.16% increment in relative oral bioavailability led to higher in vivo anti-proliferative activity manifesting 19% more inhibition than Taxotere®. Conclusively, it is revealed that the developed nanoemulsion will be a propitious approach towards alternative docetaxel therapy.

Gum Arabic-encapsulated gold nanoparticles for a non-invasive photothermal ablation of lung tumor in mice.

BACKGROUND: In our previous work, we have extensively evaluated the physiochemical characteristics of Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs; 15-18nm) and reported their effectiveness in stopping the tumor initiation via inhibiting the pre-neoplastic lesions in liver. OBJECTIVE: The rationale of this study is to detect the efficiency of using GA-AuNPs in photothermal application as a non-invasive technique against lung tumor. We investigated the cytotoxicity of GA-AuNPs on A549 cells, and then studied their apoptotic, anti-inflammatory, lipid peroxidation and anti-neovascular effect in in vivo model using a chemically-induced lung cancer in mice. The histopathological changes due to GA-AuNPs were investigated. RESULTS: In the presence of laser irradiation, GA-AuNPs had a considerable cytotoxicity against A549 cells. The treatment of lung tumor-bearing mice with GA-AuNPs followed by laser exposure enhanced the apoptotic pathway and this was obvious from the histopathological investigations and the elevations in cytochrome-c, death receptor 5 and the subsequent upregulation of caspase-3, we also reported a significant reduction in the levels of the inflammatory mediator TNF-α and the angiogenesis inducer VEGF. An induction of lipid peroxidation was also reported upon treatment with either GA or GA-AuNPs. CONCLUSION: GA-AuNPs showed no cytotoxicity in the absence of light, however the combination of GA-AuNPs with laser induced cell death in lung tumor tissues with a reduction in the inflammation and angiogenesis together with an elevation in lipid peroxidation, suggesting the potential use of these functionalized nanoparticles as a promising photothermal non-invasive treatment modality.

Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice.

This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA-AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA-AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA-AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.

Development of a pluripotent ES-like cell line from Asian sea bass (Lates calcarifer)--an oviparous stem cell line mimicking viviparous ES cells.

We report a pluripotent embryonic stem cell-like cell line designated as SBES from blastula stage embryos of Asian sea bass (Lates calcarifer), which is an economically important cultivable and edible marine fish species in India. The SBES cells were cultured at 28 degrees C in Leibovitz L-15 medium supplemented with 20% fetal bovine serum without a feeder layer. The ES-like cells were round or polygonal and grew exponentially in culture. The SBES cells exhibited an intense alkaline phosphatase activity and expression of transcription factor Oct 4. The undifferentiated state of these cells was maintained at low seeding densities and the cells formed embryoid bodies when seeded in bacteriological plates. On treatment with all-trans retinoic acid, these cells differentiated into neuron-like cells, muscle cells, and beating cardiomyocytes, indicating their pluripotency. This embryonic ES-like cell line derived from an oviparous fish blastula conserved several peculiar features of viviparous mammalian embryonic stem cell lines. The present study highlights the importance and potential of piscine ES-like cell line for stem cell research without evoking ethical issues and invasive interventions sparing mammalian embryos.