Antibacterial and Antioxidant Compounds from the Root Extract of Aloe debrana.

This study was conducted to isolate and identify the chemical compounds from the roots of Aloe debrana (L.) and evaluate their antioxidant and antibacterial activities. From the acetone (99.5%) extract of the roots of this plant, four anthraquinones, such as chrysophanol (1), asphodeline (2), aloesaponarin I (5), and laccaic acid D-methyl ester (6), and a new catechol derivative, 5-allyl-3-methoxybenzene-1,2-diol (3), were isolated and elucidated by different chromatographic and spectroscopic methods together with linoleic acid (4), respectively. Compounds 2, 3, and 4 were reported here for the first time from this plant and compound 3 from the genus Aloe. The compounds were evaluated for their antioxidant activity using H2O2 and DPPH assays and bactericidal activity against S. aureus and E. coli. Compounds 3 and 6 showed highest antioxidant activities with IC50 values of 19.38 ± 0.64 and 32.81 ± 0.78 µg/mL in DPPH, and 28.52 ± 1.08 and 27.31 ± 1.46 µg/mL in H2O2, respectively. The isolated compounds also demonstrated considerable activity towards S. aureus. Among these compounds, compound 3 exhibited the highest activity (91.20 ± 0.12% and 9.14 ± 0.93 mm at 1.0 mg/mL) against this bacterium. The overall results suggest that the isolated compounds may be considered as potential sources of the bioactive agents to be used in the pharmacological, food, and other industries. Moreover, their high sensitivity against S. aureus may also support the use of A. debrana plant in the traditional medicine to treat wounds. Therefore, the isolated compounds are responsible for medicinal properties of this plant.

Recent Contributions of Mass Spectrometry-Based "Omics" in the Studies of Breast Cancer.

Breast cancer (BC) is one of the most heterogeneous groups of cancer. As every biotype of BC is unique and presents a particular "omic" signature, they are increasingly characterized nowadays with novel mass spectrometry (MS) strategies. BC therapeutic approaches are primarily based on the two features of human epidermal growth factor receptor 2 (HER2) and estrogen receptor (ER) positivity. Various strategic MS implementations are reported in studies of BC also involving data independent acquisitions (DIAs) of MS which report novel differential proteomic, lipidomic, proteogenomic, phosphoproteomic, and metabolomic characterizations associated with the disease and its therapeutics. Recently many "omic" studies have aimed to identify distinct subsidiary biotypes for diagnosis, prognosis, and targets of treatment. Along with these, drug-induced-resistance phenotypes are characterized by "omic" changes. These identifying aspects of the disease may influence treatment outcomes in the near future. Drug quantifications and characterizations are also done regularly and have implications in therapeutic monitoring and in drug efficacy assessments. We report these studies, mentioning their implications toward the understanding of BC. We briefly provide the MS instrumentation principles that are adopted in such studies as an overview with a brief outlook on DIA-MS strategies. In all of these, we have chosen a model cancer for its revelations through MS-based "omics".

Antibacterial and antibiofilm effects of Pseudomonas aeruginosa derived outer membrane vesicles against Streptococcus mutans.

Antimicrobial resistance (AMR) is a serious and most urgent global threat to human health. AMR is one of today's biggest difficulties in the health system and has the potential to harm people at any stage of life, making it a severe public health issue. There must be fewer antimicrobial medicines available to treat diseases given the rise in antibiotic-resistant organisms. If no new drugs are created or discovered, it is predicted that there won't be any effective antibiotics accessible by 2050. In most cases, Streptococcus increased antibiotic resistance by forming biofilms, which account for around 80 % of all microbial infections in humans. This highlights the need to look for new strategies to manage diseases that are resistant to antibiotics. Therefore, development alternative, biocompatible and high efficacy new strategies are essential to overcome drug resistance. Recently, bacterial derived extracellular vesicles have been applied to tackle infection and reduce the emergence of drug resistance. Therefore, the objective of the current study was designed to assess the antibacterial and antibiofilm potential of outer membrane vesicles (OMVs) derived from Pseudomonas aeruginosa againstStreptococcus mutans. According to the findings of this investigation, the pure P. aeruginosa outer membrane vesicles (PAOMVs) display a size of 100 nm. S. mutans treated with PAOMVs showed significant antibacterial and antibiofilm activity. The mechanistic studies revealed that PAOMVs induce cell death through excessive generation of reactive oxygen species and imbalance of redox leads to lipid peroxidation, decreased level of antioxidant markers including glutathione, superoxide dismutase and catalase. Further this study confirmed that PAOMVs significantly impairs metabolic activity through inhibiting lactate dehydrogenase activity (LDH), adenosine triphosphate (ATP) production, leakage of proteins and sugars. Interestingly, combination of sub-lethal concentrations of PAOMVs and antibiotics enhances cell death and biofilm formation of S. mutans. Altogether, this work, may serve as an important basis for further evaluation of PAOMVs as novel therapeutic agents against bacterial infections.

Chitosan-PEI passivated carbon dots for plasmid DNA and miRNA-153 delivery in cancer cells.

These days carbon dots have been developed for multiple biomedical applications. In the current study, the transfection potential of synthesized carbon dots from single biopolymers such as chitosan, PEI-2kDa, and PEI-25kDa (CS-CDs, PEI2-CDs, and PEI25-CDs) and by combining two biopolymers (CP2-CDs and CP25-CDs) through a bottom-up approach have been investigated. The characterization studies revealed successful synthesis of fluorescent, positively charged carbon dots <20 nm in size. Synthesized carbon dots formed a stable complex with plasmid DNA (EGFP-N1) and miRNA-153 that protected DNA/miRNA from serum-induced degradation. In-vitro cytotoxicity analysis revealed minimal cytotoxicity in cancer cell lines (A549 and MDA-MB-231). In-vitro transfection of EGFP-N1 plasmid DNA with PEI2-CDs, PEI25-CDs and CP25-CDs demonstrated that these CDs could strongly transfect A549 and MDA-MB-231 cells. The highest EGFP-N1 plasmid transfection efficiency was observed with PEI2-CDs at a weight ratio of 32:1. PEI25-CDs polyplex showed maximum transfection at a weight ratio of 8:1 in A549 at a weight ratio of 16:1 in MDA-MB-231 cells. CP25-CDs exhibited the highest transfection at a weight ratio of 16:1 in both cell lines. The in-vitro transfection of target miRNA, i.e., miR-153 in A549 and MDA-MB-231 cells with PEI2-CDs, PEI25-CDs, and CP25-CDs suggested successful transfer of miR-153 into cells which induced significant cell death in both cell lines. Importantly, CS-CDs and CP2-CDs could be tolerated by cells up to 200 µg/mL concentration, while PEI2-CDs, PEI25-CDs, and CP25-CDs showed non-cytotoxic behavior at low concentrations (25 µg/mL). Together, these results suggest that a combination of carbon dots synthesized from chitosan and PEI (CP25-CDs) could be a novel vector for transfection nucleic acids that can be utilized in cancer therapy.

pH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy.

Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.

The eco-friendly treatment of rubber industry effluent by using adsorbent derived from Moringa oleifera bark and Pseudomonas sp, cultured from effluent.

Rubber processing generates a large volume of wastewater containing rubber latex residues and chemicals. Remediation of the wastewater needs a cost-effective and environment-friendly treatment method. For this study, Moringa oleifera stem bark and Pseudomonas sp. bacteria were used for adsorption and microbial treatment of the effluent. The adsorbent surface was mostly amorphous with crystallinity index 37.9% and the BET surface area was 6.622 m2/g. FTIR analysis indicated involvement of O-H stretching, ketone α, ß-unsaturated, C-H stretching, carboxylic acid and derivatives O-C stretching functional groups in the adsorption process. The assessment of the above two agents was based on their reduction capabilities of the toxic parameters, such as total suspended and dissolved solids, total solids, biological and chemical oxygen demand, sulphate, ammonium, dissolved oxygen, phosphate, pH, electrical conductivity, turbidity, and oxidation reduction potential from the wastewater. A comparative study of the present work revealed that both the agents were effective in reduction of most of the above parameters below the safe discharge limits. However, the adsorption using Moringa oleifera stem bark was better compared to the biodegradation by Pseudomonas sp. bacteria. The main challenges that typically accompany biodegradation include microbe handling and a lower removal percentage than adsorption.

Fabrication of phenyl boronic acid modified pH-responsive zinc oxide nanoparticles as targeted delivery of chrysin on human A549 cells.

Recently, different natural bioactive compounds have been used as anticancer agents for their various therapeutic benefits and non-toxic nature to other organs. However, they have various restrictions in preclinical and clinical studies due to their non-targeting nature and insufficient bioavailability. As a result, a zinc oxide nanoparticle (ZnO) based drug delivery medium was constructed which has good bio-compatibility and bio-degradability. It also displays cancer cell-specific drug delivery in a targeted and controlled way. In the present study, phenylboronic acid (PBA) tagged ZnO nanoparticles (ZnO-PBA) was fabricated and in the next step, chrysin (a natural bio-active molecule) was loaded to it to form the nanoconjugate (ZnO-PBA-Chry). Different characterization techniques were used to confirm the successful fabrication of ZnO-PBA-Chry. PBA-tagging to the nanoparticle helps in targeted delivery of chrysin in lung cancer cells (A549) as PBA binds with sialic acid receptors which are over-expressed on the surface of A549 cells. As ZnO dissociates in acidic pH, it shows stimuli-responsive release of chrysin in tumor microenvironment. Application of ZnO-PBA-Chry nanohybrid in lung cancer cell line A549 caused oxidative stress mediated intrinsic cell death and cell cycle arrest. ZnO-PBA-Chry downregulated MMP-2 and VE-Cadherin, thereby inhibiting metastasis and the invasive property of A549 cells.

Enhancement of anti-neoplastic effects of cuminaldehyde against breast cancer via mesoporous silica nanoparticle based targeted drug delivery system.

AIMS: Synthesis of novel drug delivery system for targeted delivery of cuminaldehyde to breast cancer cells and the subsequent analyses of anti-neoplastic potential of the drug. MAIN METHODS: 3-carboxy-phenyl boronic acid (PBA) conjugated and polyacrylic acid (PAA) gated mesoporous silica nanoparticles (MSNs) were synthesized for the targeted delivery of cuminaldehyde (CUM) to breast cancer cells. Enhancement of anti-neoplastic effects of cuminaldehyde (4-isopropylbenzaldehyde) by the nanoconjugates was assessed. KEY FINDINGS: The anti-cancer effects of non-targeted and targeted drug-nanoconjugates were examined in vitro and in vivo. The targeted drug-nanoconjugates caused cell cycle arrest and induced the intrinsic pathway of apoptosis in MCF-7 cells through mitochondrial damage. In vivo intravenous injection of the targeted drug-nanoconjugates led to effective reduction in growth of 4 T1 induced mammary pad tumor in female BALB/c mice via augmented accumulation of cuminaldehyde. The drug-nanoconjugates did not exhibit any systemic toxicity. SIGNIFICANCE: Therefore, MSN-PBA-CUM-PAA represents a potent therapeutic model for breast cancer treatment.

Self Nano-Emulsifying Curcumin (SNEC30) attenuates arsenic-induced cell death in mice.

Several precedents have confirmed numerous infirmities caused by arsenic poisoning, including immune suppression and cancer. Exposure to arsenic leads to alterations of the cellular machinery and eventually cell death, depending on the dose and duration of exposure. Oxidative stress induced by arsenic is the major mechanism by which it inflicts cellular toxicity, challenging the survival-support - autophagy and culminating in apoptosis in the thymus and spleen of mice. Curcumin, a potent dietary anti-oxidant with known anti-apoptotic and anti-inflammatory properties, was assessed for therapeutic benefits. However, the major caveat of this polyphenol is its low water solubility and limited bioavailability. Therefore, Self Nano-Emulsifying Curcumin (SNEC30) was used to treat mice exposed to arsenic. When administered, SNEC30 effectively ameliorated the adverse effects of arsenic in mice, by restoring structural alterations and reducing ROS-mediated cell death, thereby endorsing the importance of nutraceuticals in counteracting heavy metal-induced cellular toxicity.

In vivo therapeutic evaluation of a novel bis-lawsone derivative against tumor following delivery using mesoporous silica nanoparticle based redox-responsive drug delivery system.

Herein, we have evaluated the in vivo therapeutic efficacy and systemic toxicity profile of a synthetic anticancer compound [3,3'-((4-(trifluoromethyl)phenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione)]. A multifunctional mesoporous silica nanoparticle (MSN) based drug delivery network was also fabricated which specifically showed targeting nature towards the cancer cell. The mesopores of silica nanoparticles were tagged with phenyl boronic acid (PBA) for targeted drug delivery into tumor tissue. 1j was then loaded inside the nanocarriers followed by pore blocking with gold nanoparticles (GN) to attain a redox-responsive controlled drug delivery pattern. The synthesized nanocarriers (1j@-MSN-PBA-GN) having mean diameter of ~86 nm exhibited a moderate 1j loading content of 13.68% with overall negative surface charge. Both the targeted and non-targeted nanoformulations were tested for their anticancer activities both in vitro and in vivo models, and found more effective as compared with free 1j treatment. However, the targeted nanoformulations showed higher therapeutic effect due to increased cellular internalization and caused mitochondria-dependent apoptosis in MCF-7 cells via oxidative stress. Besides, the targeted nanoformulation significantly inhibited in the development of solid tumor in comparison to non-targeted nanoformulations and free 1j as a consequence of increased internalization of the drug-candidate in tumor tissue. Therefore, this study proposes that 1j can be considered as a potent anti-carcinogenic compound in vivo and its therapeutic potential is further increased by using PBA functionalized and GN gated MSN-based controlled drug delivery system without showing any significant systemic toxicity.

Metal-doped and hybrid carbon dots: A comprehensive review on their synthesis and biomedical applications.

Carbon dots (CDs) are the most promising candidates of the carbon family with superior properties like ultra-small size, high aqueous solubility, low cytotoxicity, and inherent photoluminescence which makes them suitable for diverse biomedical applications. Methods have been developed to enhance their applications. Doping/surface passivation of CDs improves their physicochemical properties, visible light absorption probability, and quantum yield by controlling their size, morphology, structure, and band-gap energy. Recently, metal-doped CDs have emerged as an important class of nanomaterials with numerous biomedical applications. Additionally, the conjugation of CDs with semiconductor metal-oxide nanoparticles (NPs) enhances their free radical production rates under visible light irradiation. Conjugation of fluorescent CDs with magnetic NPs leads to the development of multimodal imaging platforms. Similarly, ternary conjugates composed of fluorescent CDs, near-infrared (NIR) responsive, and magnetic NPs are useful for multi-modal imaging-guided, and NIR-responsive synergistic chemo-phototherapy. However, no comprehensive review is published yet which covers metal-doped and hybrid CDs. Therefore, herein we provide detailed information about their synthesis and important biomedical applications. Firstly, we have covered various synthesis methods for CD conjugation including the critical analysis of the effects of the reaction conditions and doping/conjugation on the structure and properties of the CDs. Then we have extensively reviewed their biomedical applications as antimicrobial, antioxidant, and bioimaging agents, and in the field of cancer phototherapy with special emphasis on their mechanisms of actions. Finally, the future directions of research and the applications of the metal-doped and hybrid CDs have been discussed. We believe that this review article will enrich the understanding of different synthetic routes of CD-nanocomposites and their biomedical applications.

Zinc oxide nanoparticles: A comprehensive review on its synthesis, anticancer and drug delivery applications as well as health risks.

In recent years, zinc oxide nanoparticles (ZnONPs) emerged as an excellent candidate in the field of optical, electrical, food packaging and particularly in biomedical research. ZnONPs show cancer cell specific toxicity via the pH-dependent (low pH) dissolution into Zn2+ ions, which generate reactive oxygen species and induce cytotoxicity in cancer cells. Further, ZnONPs have also been used as an effective carrier for the targeted delivery of several anticancer drugs into tumor cells. The increasing focus on ZnONPs resulted in the development of various synthesis approaches including chemical, pHysical, and green or biological for the manufacturing of ZnONPs. In this article, at first we have discussed the various synthesis methods of ZnONPs and secondly its biomedical applications. We have extensively reviewed the anticancer mechanism of ZnONPs on different types of cancers considering its size, shape and surface charge dependent cytotoxicity. Photoirradiation with UV light or NIR laser further increase its anticancer activity via synergistic chemo-photodynamic effect. The drug delivery applications of ZnONPs with special emphasis on drug loading mechanism, stimuli-responsive controlled release and therapeutic effects have also been discussed in this review. Finally, its side effects to vital body organs with mechanism via different exposure routes, the future direction of the ZnONPs research and application are also discussed.

Tumor targeted delivery of umbelliferone via a smart mesoporous silica nanoparticles controlled-release drug delivery system for increased anticancer efficiency.

Herein, a mesoporous silica nanoparticle (MSN) based biocompatible, targeted and controlled drug delivery system has been synthesized for tumor tissue-specific drug delivery. Umbelliferone, a natural coumarin derivative was loaded into the pores of MSN and capped with pH-sensitive poly acrylic acid (PAA). For targeted delivery of umbelliferone in tumor tissue, folic acid (FA) was grafted onto the surface of drug-loaded and PAA-coated MSN. The successful construction of the nanohybrid (Umbe@MSN-PAA-FA) was confirmed by performing a series of characterization. The synthesized pH-responsive nanohybrid showed diameter of around 50 nm with overall negative surface charge and drug loading content of 12.56%. In vitro study showed that the nanohybrid caused significant cytotoxicity through the induction of both oxidative stress as well as mitochondrial damage in folate receptor over-expressed in human breast cancer cell, MCF-7 compared with free umbelliferone. In vivo study also exhibited that the nanohybrid effectively reduced tumor growth in tumor-bearing mice compared with free umbelliferone due to the enlarged bioavailability of the drug in tumor tissue. Besides, the nanohybrid did not exhibit any significant sign of systemic toxicity in other vital organs. Together, the study denoted that PAA and FA functionalized MSN controlled-drug delivery system could assist to increase the anticancer potential of umbelliferone.

Nanoparticles as Smart Carriers for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a promising strategy for the treatment of many forms of cancer by stimulating body's own immune system. This therapy not only eradicates tumor cells by inducing strong anti-tumor immune response but also prevent their recurrence. The clinical cancer immunotherapy faces some insurmountable challenges including high immune-mediated toxicity, lack of effective and targeted delivery of cancer antigens to immune cells and off-target side effects. However, nanotechnology offers some solutions to overcome those limitations, and thus can potentiate the efficacy of immunotherapy. This review focuses on the advancement of nanoparticle-mediated delivery of immunostimulating agents for efficient cancer immunotherapy. Here we have outlined the use of the immunostimulatory nanoparticles as a smart carrier for effective delivery of cancer antigens and adjuvants, type of interactions between nanoparticles and the antigen/adjuvant as well as the factors controlling the interaction between nanoparticles and the receptors on antigen presenting cells. Besides, the role of nanoparticles in targeting/activating immune cells and modulating the immunosuppressive tumor microenvironment has also been discussed extensively. Finally, we have summarized some theranostic applications of the immunomodulatory nanomaterials in treating cancers based on the earlier published reports.

Synthesis and biomedical applications of nanoceria, a redox active nanoparticle.

BACKGROUND: Nanoceria has recently received much attention, because of its widespread biomedical applications, including antibacterial, antioxidant and anticancer activity, drug/gene delivery systems, anti-diabetic property, and tissue engineering. MAIN BODY: Nanoceria exhibits excellent antibacterial activity against both Gram-positive and Gram-negative bacteria via the generation of reactive oxygen species (ROS). In healthy cells, it acts as an antioxidant by scavenging ROS (at physiological pH). Thus, it protects them, while in cancer cells (under low pH environment) it acts as pro-oxidant by generating ROS and kills them. Nanoceria has also been effectively used as a carrier for targeted drug and gene delivery in vitro and in vivo models. Besides, nanoceria can also act as an antidiabetic agent and confer protection towards diabetes-associated organ pathophysiology via decreasing the ROS level in diabetic subjects. Nanoceria also possesses excellent potential in the field of tissue engineering. In this review, firstly, we have discussed the different methods used for the synthesis of nanoceria as these are very important to control the size, shape and Ce3+/Ce4+ ratio of the particles upon which the physical, chemical, and biological properties depend. Secondly, we have extensively reviewed the different biomedical applications of nanoceria with probable mechanisms based on the literature reports. CONCLUSION: The outcome of this review will improve the understanding about the different synthetic procedures and biomedical applications of nanoceria, which should, in turn, lead to the design of novel clinical interventions associated with various health disorders.

Targeted delivery of quercetin via pH-responsive zinc oxide nanoparticles for breast cancer therapy.

Naturally occurring bioactive compounds are gaining much importance as anti-tumor agents in recent times due to their high therapeutic potential and less systemic toxicity. However, different preclinical and clinical studies have noted significant shortcomings, such as nonspecific tumor targeting and low bioavailability which limit their usage in therapeutics. Therefore, a safe and compatible nanoparticle mediated controlled drug delivery system is in high demand to enable effective transport of the drug candidates in the tumor tissue. Herein, we have synthesized phenylboronic acid (PBA) conjugated Zinc oxide nanoparticles (PBA-ZnO), loaded with quercetin (a bioflavonoid widely found in plants), with zeta potential around -10.2 mV and diameter below 40 nm. Presence of PBA moieties over the nanoparticle surface facilitates targeted delivery of quercetin to the sialic acid over-expressed cancer cells. Moreover, Quercetin loaded PBA-ZnO nanoparticles (denoted as PBA-ZnO-Q) showed pH responsive drug release behavior. Results suggested that PBA-ZnO-Q induced apoptotic cell death in human breast cancer cells (MCF-7) via enhanced oxidative stress and mitochondrial damage. In line with the in vitro results, PBA-ZnO-Q was found to be effective in reducing tumor growth in EAC tumor bearing mice. Most interestingly, PBA-ZnO-Q is found to reduce tumor associated toxicity in liver, kidney and spleen. The cytotoxic potential of the nanohybrid is attributed to the combinatorial cytotoxic effects of quercetin and ZnO in the cancer cells. Overall, the presented data highlighted the chemotherapeutic potential of the novel nanohybrid, PBA-ZnO-Q which can be considered for clinical cancer treatment.