Use of antioxidant nanoliposomes for co-delivery of PTEN plasmids and plumbagin to induce apoptosis in hepatic cancer cells.

Hepatocellular carcinoma remains a challenging contributor to the global cancer and related mortality, and claims approximately 800,000 deaths each year. Dysregulation or loss of function mutations involving the tumor suppressor gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN), has been well-characterized in various cancers to elicit anomalous cell proliferation and oncogenic transformation. However, the delivery and bioavailability of genes/drugs of interest to carcinomas remains a serious bottleneck behind the success of any anti-cancer formulation. In this study, we have engineered nanoliposomes containing PTEN plasmids, plumbagin, and antioxidant cerium oxide nanoparticles (Lipo-PTEN-Plum) to restore the PTEN expression and inhibit the AKT/PI3K pathway. The Lipo-PTEN-Plum was quasi-spherical in shape with ∼110 nm diameter and ∼64% plumbagin loading efficiency. The Lipo-PTEN-Plum was successfully internalized HepG2 cells, restore PTEN expression and inhibit PI3K/AKT pathway to induce death in cells grown in monolayer and in form of spheroids. Mechanistically, the formulation showed G2/M cell cycle arrest, DNA damage and apoptosis in hepatic cancer cells. Other cellular events such as Caspase-7 overexpression and PI3K (phosphoinositide 3-kinase), AKT (a serine/threonine protein kinase), PARP [Poly (ADP-ribose) polymerases], and mTOR (Mammalian target of rapamycin) inhibition led to the apoptosis in hepatic cancer cells. The mRNA expression profile of PTEN, PI3K, AKT3, Caspase-7, PARP and mTOR proteins, primarily controlling the cancer cell proliferation and apoptosis, suggest that exogenous supply of PTEN could regulate the expression of oncogenic proteins and thus cancer progression.

Nanominerals in nutrition: Recent developments, present burning issues and future perspectives.

The unusual intrinsic properties of nanomaterials, such as small size and high surface-to-volume ratio, have invited their applications in various sectors of animal and human nutrition. Since the recent past, there has been tremendous surge in demand for animal-derived foods due to the concomitant increase in human population. The quantity and quality of animal-derived foods are mainly dependent on the health and wellness of the livestock. Dietary mineral elements are well known to play essential roles in maintaining the livestock's nutrition. However, poor bioavailability of administered mineral elements leads to malnutrition and associated health issues in animals. Feeding nanoparticles to livestock has shown promising results including increased growth performance, immunity, reproduction ability, and quality of animal products. This review provides a comprehensive discussion on the need for animal nutrition, major bottlenecks of the field, and use of nanotechnologies as an alternative to the traditional pattern of mineral element supplementation. A significant emphasis has also been given to the possible approaches for developing nanominerals suitable for livestock nutrition. Availability of consumer market for nanotechnology-based food may drive this field to develop different strategies for food sensing, packaging, and nutrition.

Cultivating human tissues and organs over lab-on-a-chip models: Recent progress and applications.

In vivo models are indispensable for preclinical studies for various human disease modeling and drug screening, however, face several obstacles such as animal model species differences and ethical clearance. Additionally, it is difficult to accurately predict the organ interaction, drug efficacy, and toxicity using conventional in vitro two-dimensional (2D) cell culture models. The microfluidic-based systems provide excellent opportunity to recapitulate the human organ/tissue functions under in vitro conditions. The organ/tissue-on-chip models are one of best emerging technologies that offer functional organs/tissues on a microfluidic chip. This technology has potential to noninvasively study the organ physiology, tissue development, and diseases etymology. This chapter comprises the benifits of 2D and three-dimensional (3D) in vitro cultures as well as highlights the importance of microfluidic-based lab-on-a-chip technique. The development of different organs/tissues-on-chip models and their biomedical application in various diseases such as cardiovascular diseases, neurodegenerative diseases, respiratory-based diseases, cancers, liver and kidney diseases, etc., have also been discussed.

Novel corona virus (COVID-19) pandemic: current status and possible strategies for detection and treatment of the disease.

INTRODUCTION: In December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak occurred and caused the coronavirus disease of 2019 (COVID-19), which affected ~ 190 countries. The World Health Organization (WHO) has declared COVID-19 a pandemic on 11 March 2020. AREA COVERED: In the review, a comprehensive analysis of the recent developments of the COVID-19 pandemic has been provided, including the structural characterization of the virus, the current worldwide status of the disease, various detection strategies, drugs recommended for the effective treatment, and progress of vaccine development programs by different countries. This report was constructed by following a systematic literature search of bibliographic databases of published reports of relevance until 1 September 2020. EXPERT OPINION: Currently, the countries are opening businesses despite a spike in the number of COVID-19 cases. The pharmaceutical industries are developing clinical diagnostic kits, medicines, and vaccines. They target different approaches, including repurposing the already approved diagnosis and treatment options for similar CoVs. At present, over ~200 vaccine candidates are being developed against COVID-19. Future research may unravel the genetic variations or polymorphisms that dictate these differences in susceptibilities to the disease.

Calcium carbonate nano- and microparticles: synthesis methods and biological applications.

Calcium carbonate micro- and nanoparticles are considered as chemically inert materials. Therefore, they are widely considered in the field of biosensing, drug delivery, and as filler material in plastic, paper, paint, sealant, and adhesive industries. The unusual properties of calcium carbonate-based nanomaterials, such as biocompatibility, high surface-to-volume ratio, robust nature, easy synthesis, and surface functionalization, and ability to exist in a variety of morphologies and polymorphs, make them an ideal candidate for both industrial and biomedical applications. Significant research efforts have been devoted for developing novel synthesis methods of calcium carbonate particles in micrometer and nanometer dimensions. This review highlights different approaches of the synthesis of calcium carbonate micro- and nanoparticles, such as precipitation, slow carbonation, emulsion, polymer-mediated method, including in-situ polymerization, mechano-chemical, microwave-assisted method, and biological methods. The applications of these versatile calcium carbonate micro- and nanoparticles in the biomedical field (such as in drug delivery, therapeutics, tissue engineering, antimicrobial activity, biosensing applications), in industries, and environmental sector has also been comprehensively covered.

Site-specific delivery of a natural chemotherapeutic agent to human lung cancer cells using biotinylated 2D rGO nanocarriers.

Chemotherapy has remained one of the most commonly employed treatment modalities for cancer. Despite the clinical availability of a large number of chemotherapeutic agents, the uncontrolled systemic distribution and the associated harmful side effects of chemotherapeutic agents pose major challenges demanding concerted efforts to enhance their cancer targetability. The layered structure of two-dimensional (2D) materials offers new opportunities by increasing the drug pay-load influencing the drug-release kinetics in a cancer micro-environment and facilitating targetability through the large accessible surface area. To investigate such potential benefits of 2D materials, we have developed a biocompatible targeted 2D drug delivery system using graphene oxide (GO) as a model nanocarrier (NC) that could hold a high concentration of gallic acid (GA), a natural chemotherapeutic agent found in green tea. Interestingly, the antioxidant nature of GA also reduced GO to a high-quality few-layered thin reduced-graphene oxide (rGO) during drug loading while forming rGO nanocarrier (rGONC). The biotinylated rGONC further improved their targetability to A549 human lung carcinoma cells and they enhanced cellular internalization efficiency. From these targeted 2D NCs, the drug could release only slowly at the physiological pH but liberated rapidly at lower pH encountered by the tumor microenvironment resulting in significant toxicity toward the lung carcinoma cells. As such, this work opens up new possibilities for employing 2D materials for targeted chemotherapeutic applications.

Serotonin-Stearic Acid Bioconjugate-Coated Completely Biodegradable Mn3O4 Nanocuboids for Hepatocellular Carcinoma Targeting.

In this study, a serotonin-stearic acid (ST-SA)-based bioconjugate was synthesized for the surface modification of manganese oxide-based nanocuboids (MNCs) for delivering of anticancer drug (i.e., doxorubicin hydrochloride (DOX)) to human liver cancer cells. MNCs were synthesized by chemical precipitation method, and their surface was modified with ST-SA bioconjugate for targeting of MNCs to cancer cells. The ST-SA@MNCs along with DOX showed good colloidal stability, high drug encapsulation (98.3%), and drug loading efficiencies (22.9%) as well as pH-responsive biodegradation. Coating with ST-SA conjugate provided a shield to MNCs which sustained their degradation in an acidic environment. The release of DOX was higher (81.4%) in acidic media than under the physiological conditions (20.5%) up to 192 h. The in vitro anti-proliferation assay showed that ST-SA@MNCs exhibit higher cell growth inhibition compared to that of pure DOX after 48 h of treatment. The cellular uptake and apoptosis studies revealed the enhanced uptake of ST-SA@MNCs in contrast to the MNCs due to overexpressed ST receptor on hepatocellular carcinoma cells and triggered the generation of reactive oxygen species in the cells. Therefore, these results indicated that the DOX-loaded, ST-SA stabilized MNCs improved the therapeutic index of DOX and would be a promising therapeutic candidate for tumor therapy.

Co-delivery of AKT3 siRNA and PTEN Plasmid by Antioxidant Nanoliposomes for Enhanced Antiproliferation of Prostate Cancer Cells.

Globally, prostate cancer is the fifth major cancer type and the second leading cause of cancer-related death in men. In 2018, about 1.3 million prostate cancer cases were reported worldwide. It is reported that loss of PTEN (tumor suppressor gene) expression leads to hyperactivation of the PI3K/AKT pathway and thus induces uncontrolled cell proliferation. Loss or mutation in regular PTEN expression is reported to occur in ∼30% of primary prostate cancer cases and ∼65% of metastatic cancer cases. Restoring the PTEN expression could inhibit the PI3K/AKT/mTOR signaling pathway, thus avoid the growth of prostate cancer cells. In this work, we have synthesized a multifunctional nanoliposomal formulation incorporating PTEN plasmid, AKT3 siRNA, and antioxidant cerium oxide nanoparticles (CeNPs). The nanoliposomes were able to successfully internalize in prostate cancer (PC-3) cells, restore the expression of PTEN protein, and knock down AKT3 mRNA. Further, the multifunctional nanoliposomes induce DNA damage and apoptosis in prostate cancer cells. The investigation of the PI3K/AKT/mTOR signaling pathway revealed that PTEN protein and apoptosis-specific proteins are overexpressed, leading to the inhibition of oncoproteins and, thus, prostate cancer.

Unveiling the effect of 11-MUA coating on biocompatibility and catalytic activity of a gold-core cerium oxide-shell-based nanozyme.

The biocompatibility and catalytic activity of nanomaterials exhibiting biological enzyme-like functions (nanozymes) are controlled by shape, size, composition, and surface capping molecules. Although synthesis of multifunctional nanozymes for multiple applications has shown tremendous attraction among researchers worldwide, often their biocompatibility is compromised. In this work, we report the replacement of CTAB by 11-MUA from the surface of a Au-core CeO2-shell NP-based nanozyme studied for exhibiting multiple enzyme-like activities such as peroxidase, catalase, and superoxide dismutase. We compared the biocompatibility and enzyme-like activities of CTAB coated Au-core CeO2-shell NPs (CSNPs) before and after 11-MUA coating. The catalytic reaction mechanism of peroxidase-like activity of CTAB coated CSNPs was found to be the "Random Bi-Bi", which also remained unaltered after removal of surface CTAB with 11-MUA. The other kinetic parameters, K m and V max values, of 11-MUA coated CSNPs were found to be comparable to the CTAB coated NPs.

Multifunctional antioxidant nanoliposome-mediated delivery of PTEN plasmids restore the expression of tumor suppressor protein and induce apoptosis in prostate cancer cells.

Prostate cancer is the second leading cause of cancer death in men and about one in nine will be diagnosed in his lifetime. Loss of PTEN has been considered as one of the major factors leading to the origin of prostate cancer through modulating PI3K/AKT signaling pathways. In this study, we have prepared a multifunctional antioxidant nanoliposome containing PTEN plasmid and cerium oxide nanoparticles (CeNPs). The efficient delivery of PTEN plasmid to human prostate cancer cells (PC-3) leads to restoration of the expression of lost PTEN protein in the cell cytoplasm. The delivered superoxide dismutase (SOD)-mimetic CeNPs were also found to decrease the cytoplasmic free radical levels in prostate cancer cells. The above two activities induced DNA fragmentation and micronucleus formation in prostate cancer cells. Furthermore, it was also found that these multifunctional antioxidant nanoliposomes inhibit the PI3K/AKT signaling pathway to negatively regulate the cell viability of prostate cancer cells. The mRNA expression pattern of other relevant proteins predominantly involved in cancer cell proliferation and apoptosis suggested that the high PTEN expression could control the synthesis of oncogenic proteins. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3152-3164, 2018.

Gold core/ceria shell-based redox active nanozyme mimicking the biological multienzyme complex phenomenon.

Catalytically active individual gold (Au) and cerium oxide (CeO2) nanoparticles (NPs) are well known to exhibit specific enzyme-like activities, such as natural catalase, oxidase, superoxide dismutase, and peroxidase enzymes. These activities have been maneuvered to design several biological applications such as immunoassays, glucose detection, radiation and free radical protection and tissue engineering. In biological systems, multienzyme complexes are involved in catalyzing important reactions of essential metabolic processes such as respiration, biomolecule synthesis, and photosynthesis. It is well known that metabolic processes linked with multienzyme complexes offer several advantages over reactions catalyzed by individual enzymes. A functional nanozyme depicting multienzyme like properties has eluded the researchers in the nanoscience community for the past few decades. In the current report, we have designed a functional multienzyme in the form of Gold (core)-CeO2 (shell) nanoparticles (Au/CeO2 CSNPs) exhibiting excellent peroxidase, catalase, and superoxide dismutase enzyme-like activities that are controlled simply by tuning the pH. The reaction kinetic parameters reveal that the peroxidase-like activity of this core-shell nanozyme is comparable to natural horseradish peroxidase (HRP) enzyme. Unlike peroxidase-like activity exhibited by other nanomaterials, Au/CeO2 CSNPs showed a decrease in hydroxyl radical formation, suggesting that the biocatalytic reactions are performed by efficient electron transfers. A significant enzyme-like activity of this core-shell nanoparticle was conserved at extreme pH (2-11) and temperatures (up to 90 °C), clearly suggesting the superiority over natural enzymes. Further, the utility of peroxidase-like activity of this core-shell nanoparticles was extended for the detection of glucose, which showed a linear range of detection between (100 µM to 1 mM). It is hypothesized that the proximity of the redox potentials of Au+/Au and Ce (III)/Ce (IV) may result in a redox couple promoting the multienzyme activity of core-shell nanoparticles. Au/CeO2 CSNPs may open new directions for development of single platform sensors in multiple biosensing applications.