Exploring the cytotoxicity of dinuclear Ru(II) p-cymene complexes appended N,N'-bis(4-substituted benzoyl)hydrazines: insights into the mechanism of apoptotic cell death.

Cancer is a perilous life-threatening disease, and attempts are constantly being made to create multinuclear transition metal complexes that could lead to the development of potential anticancer medications and administration procedures. Hence, this work aims to design, synthesize, characterize, and assess the anticancer efficacy of ruthenium p-cymene complexes incorporating N,N'-bis(4-substituted benzoyl)hydrazine ligands. The formation of the new complexes (Ru2H1-Ru2H3) has been thoroughly established by elemental analysis, and FT-IR, UV-vis, NMR, and HR-MS spectral techniques. The solid-state molecular structures of the complexes Ru2H1 and Ru2H3 have been determined using the SC-XRD study, which confirms the N, O, and Cl-legged piano stool pseudo-octahedral geometry of each ruthenium(II) ion. The stability of these complexes in the solution state and their lipophilicity profile have been determined. Furthermore, the title complexes were tested for their in vitro anticancer activity against cancerous H460 (lung cancer cells), SkBr3 (breast cancer cells), HepG2 (liver cancer cells), and HeLa (cervical cancer cells) along with non-cancerous (HEK-293) cells. The IC50 results revealed that complex Ru2H3 exhibits potent activity against the proliferation of all four cancer cells and outscored the effect of the standard metallodrug cisplatin. This may be attributed to the presence of a couple of lipophilic electron-donating methoxy groups in the ligand scaffold and also the ruthenium(II) p-cymene motifs. Advantageously, all the complexes (Ru2H1-Ru2H3) displayed cytotoxic specificity only towards cancerous cells by leaving the off-target non-cancerous cells undamaged. Acridine orange/ethidium bromide (AO/EB) staining, Hoechst 33342, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) staining assays were used to investigate the apoptotic pathway and ROS levels in mitochondria. The results of western blot analysis confirmed that the complexes triggered apoptosis through an intrinsic mitochondrial pathway by upregulating Bax and downregulating Bcl-2 proteins. Finally, the extent of apoptosis triggered by the complex Ru2H3 was quantified with the aid of flow cytometry using the Annexin V-FITC/propidium iodide (PI) double-staining technique.

Revisiting the Definition of 'Healthy' Participants in Substantiation of Structure/Function Claims for Dietary Supplements.

Concepts and definitions of 'healthy' have been evolving within clinical treatment algorithms as well as reference standards such as Body Mass Index and Dietary Reference Intakes. Consumers' perception of the word 'healthy' is also changing to reflect longer life span, need to stay active and in a good state of mental well-being while managing multiple diseases. Guidelines from the US Food and Drug Administration indicate that substantiating evidence for support of Structure/Function (S/F) claims for dietary supplements is best derived from clinical research conducted in a 'healthy' population. S/F claims cannot be represented to diagnose, treat, cure or prevent any disease. However, in this context, the term 'healthy' is non-descriptive and largely interpreted as an absence of disease. Guidelines for treatment of disease have been broadened to include biomarkers of disease risk such that the pool of 'healthy' volunteers eligible to be enrolled in clinical trials for S/F claim substantiation is greatly diminished. This perspective presents the challenges faced by the food and dietary supplement industry and by researcher efforts designed to substantiate S/F claims and suggest the phrase 'physiologically stable' or 'apparently healthy' as descriptions better suited to replace the term 'healthy.'

Naphthoyl benzhydrazine-decorated binuclear arene Ru(II) complexes as anticancer agents targeting human breast cancer cells.

Breast cancer is the most dangerous type in women and its fatality rate has increased over the past decade. To develop more potent and target-specific breast cancer drugs, six arene ruthenium(II) complexes (1-6) containing naphthoyl benzhydrazine ligands (NL1-NL3) were synthesized and characterized by analytical and spectroscopic (infrared, UV-visible, NMR and HR-MS) methods. The SC-XRD analysis of 1 and 6 demonstrates the bis N^O bidentate binding nature of ligands to ruthenium ions and a pseudo-octahedral geometry around the Ru(II) ion. Solution stability studies using UV-Vis spectroscopy evidenced the instantaneous hydrolysis of the complexes to form monoaquated species in a solution of 1 : 9 (v/v) DMSO/phosphate buffer. All the complexes were screened for their in vitro antiproliferative activities against different human breast cancer cells, including MCF-7, SkBr3, MDA-MB-468, MDA-MB-231, and non-cancerous HEK-293 cells, by an MTT assay, and they displayed good cancer cell growth inhibitory capacity with low IC50 values. Notably, complexes 2 and 5 comprising methoxy and p-cymene groups exhibited excellent cytotoxicity towards SkBr3 cells compared to clinical drug cisplatin. AO-EB and HOECHST-33342 staining assays revealed apoptotic morphological changes in complex-treated cancer cells. Further, reactive oxygen species and mitochondrial membrane potential assays validated that the complexes induce apoptotic cell death via an intrinsic mitochondrial pathway with ROS production. In addition, the apoptotic induction and the quantification of late apoptosis were established with the aid of western blot and flow cytometry analysis, respectively.

Impact of Surface Charge-Tailored Gold Nanorods for Selective Targeting of Mitochondria in Breast Cancer Cells Using Photodynamic Therapy.

Herein, the impact of surface charge tailored of gold nanorods (GNRs) on breast cancer cells (MCF-7 and MDA-MB-231) upon conjugation with triphenylphosphonium (TPP) for improved photodynamic therapy (PDT) targeting mitochondria was studied. The salient features of the study are as follows: (i) positive (CTAB@GNRs) and negative (PSS-CTAB@GNRs) surface-charged gold nanorods were developed and characterized; (ii) the mitochondrial targeting efficiency of gold nanorods was improved by conjugating TPP molecules; (iii) the conjugated nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) were evaluated for PDT in the presence of photosensitizer (PS), 5-aminolevulinic acid (5-ALA) in breast cancer cells; (iv) both nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) induce apoptosis, damage DNA, generate reactive oxygen species, and decrease mitochondrial membrane potential upon 5-ALA-based PDT; and (v) 5-ALA-PDT of two nanoprobes (TPP-CTAB@GNRs and TPP-PSS-CTAB@GNRs) impact cell signaling (PI3K/AKT) pathway by upregulating proapoptotic genes and proteins. Based on the results, we confirm that the positively charged (rapid) nanoprobes are more advantageous than their negatively (slow) charged nanoprobes. However, depending on the kind and degree of cancer, both nanoprobes can serve as efficient agents for delivering anticancer therapy.

Challenging refractory type B lactic acidosis in gastric adenocarcinoma-a successfully managed case.

Type B lactic acidosis is a rare complication of gastric adenocarcinoma and is associated with poor prognosis. Very few cases have been reported in the literature. A 48-year-old female presented with recurrent episodes of vomiting, loss of appetite and loss of weight for 1 month duration. Endoscopy and subsequent biopsy revealed poorly differentiated adenocarcinoma at the pyloric antrum causing gastric outflow obstruction. Contrast enhanced computed tomography scan of the chest, abdomen and pelvis revealed a malignant neoplasm of the pylorus with no distant metastasis. She developed refractory lactic acidosis not responding to medical treatment. Distal gastrectomy with limited lymph node clearance was done and lactic acidosis improved. Pathophysiology of type B lactic acidosis in solid organ malignancies can be due to the rapid turnover of cells inducing anaerobic glycolysis, thiamine deficiency and extensive hepatic metastasis. This patient did not have hepatic metastasis. This is a successful, surgically managed case of type B lactic acidosis in a patient with gastric adenocarcinoma so far reported in the region. Type B lactic acidosis is very rare in gastric cancer. Patients with refractory lactic acidosis should bring about high suspicion of solid organ malignancies and good clinical outcomes can be obtained by the reduction of tumour burden.

Spectroscopic analysis of photoneutrons in intense γ-ray background.

CR-39 SSNTD is used to measure the photoneutron spectrum produced by a medical linear accelerator in an intense γ-ray background. The spectroscopic resolution and the neutron detection threshold have been improved by introducing the event selection criteria, based on the track diameter-brightness correlation. The CR-39 detector's efficiency is determined by adapting the 1H(n,el) cross section from the ENDF/B-VIII.0 evaluations. The measured spectrum was reproduced through Talys-1.96 calculations by implementing the Gogny-HFB microscopic level density model.

Association of viral kinetics, infection history, NS1 protein with plasma leakage among Indonesian dengue infected patients.

OBJECTIVES: Plasma leakage, a hallmark of disease in Dengue virus (DENV) infection, is an important clinical manifestation and is often associated with numerous factors such as viral factors. The aim of this study is to investigate the association of virus serotype, viral load kinetics, history of infection, and NS1 protein with plasma leakage. METHODS: Subjects with fever ≤ 48 hours and positive DENV infection were included. Serial laboratory tests, viral load measurements, and ultrasonography examination to assess plasma leakage were performed. RESULTS: DENV-3 was the most common serotype found in the plasma leakage group (35%). Patients with plasma leakage demonstrated a trend of higher viral load and a longer duration of viremia compared to those without. This was significantly observed on the fourth day of fever (p = 0.037). We found higher viral loads on specific days in patients with plasma leakage in both primary and secondary infections compared to those without. In addition, we also observed more rapid viral clearance in patients with secondary infection. NS1 protein, especially after 4 days of fever, was associated with higher peak viral load level, even though it was not statistically significant (p = 0.470). However, pairwise comparison demonstrated that peak viral load level in the group of patients with circulating NS1 detected for 7 days was significantly higher than the 5-day group (p = 0.037). CONCLUSION: DENV-3 was the most common serotype to cause plasma leakage. Patients with plasma leakage showed a trend of higher viral load and a longer duration of viremia. Higher level of viral load was observed significantly on day 5 in patients with primary infection and more rapid viral clearance was observed in patients with secondary infection. Longer duration of circulating NS1 protein was also seen to be positively correlated with higher peak viral load level although not statistically significant.

Triphenylphosphonium conjugated gold nanotriangles impact Pi3K/AKT pathway in breast cancer cells: a photodynamic therapy approach.

Although gold nanoparticles based photodynamic therapy (PDT) were reported to improve efficacy and specificity, the impact of surface charge in targeting cancer is still a challenge. Herein, we report gold nanotriangles (AuNTs) tuned with anionic and cationic surface charge conjugating triphenylphosphonium (TPP) targeting breast cancer cells with 5-aminoleuvinic acid (5-ALA) based PDT, in vitro. Optimized surface charge of AuNTs with and without TPP kill breast cancer cells. By combining, 5-ALA and PDT, the surface charge augmented AuNTs deliver improved cellular toxicity as revealed by MTT, fluorescent probes and flow cytometry. Further, the 5-ALA and PDT treatment in the presence of AuNTs impairs cell survival Pi3K/AKT signaling pathway causing mitochondrial dependent apoptosis. The cumulative findings demonstrate that, cationic AuNTs with TPP excel selective targeting of breast cancer cells in the presence of 5-ALA and PDT.

Deregulation of miR-375 Inhibits HOXA5 and Promotes Migration, Invasion, and Cell Proliferation in Breast Cancer.

Breast cancer (BC) is a highly aggressive tumour and one of the women's leading causes of cancer-related deaths in worldwide. MiR-375 overexpressed in BC cells, and its biological relevance is largely unknown. Here in, we explored the function of miR-375 in BC. MicroRNA-375 targets were predicted by online target prediction tools and found that HOXA5 is one of the potential targets. MTT assay was employed to assess the effect of miR-375 on cell proliferation, where migration and invasion transwell assays were applied to detect cell migratory and invasive ability. Besides, relative expression of miR-375 and HOXA5 was measured in BC and HEK-293 cells, and its downstream gene target expressions were evaluated by qRT-PCR and western blot. In this study, we found that miR-375 expression was higher in BC cell lines than in the HEK-293 cell line, whereas HOXA5 expression was significantly lower. Our study showed that exogenous inhibition of miR-375 promoted HOXA5 expression; on the contrary, miR-375 mimics down-regulated HOXA5 expression level. Knockdown of miR-375 expression in BC cells reduces cell proliferation, migration, and invasion by inverse correlation expression of HOXA5. Our findings associated that miR-375 accelerated apoptosis evasion, proliferation, migration, and invasion by targeting HOXA5. In addition, nucleolin interferes in miR-375 biogenesis while silencing of nucleolin significantly reduced miR-375 expression and increased HOXA5 expression in BC. Thus, miR-375/HOXA5 axis may represent a potential therapeutic target for BC treatment.

Dysregulation of miRISC Regulatory Network Promotes Hepatocellular Carcinoma by Targeting PI3K/Akt Signaling Pathway.

Hepatocellular carcinoma (HCC) remains the third leading malignancy worldwide, causing high mortality in adults and children. The neuropathology-associated gene AEG-1 functions as a scaffold protein to correctly assemble the RNA-induced silencing complex (RISC) and optimize or increase its activity. The overexpression of oncogenic miRNAs periodically degrades the target tumor suppressor genes. Oncogenic miR-221 plays a seminal role in the carcinogenesis of HCC. Hence, the exact molecular and biological functions of the oncogene clusters miR-221/AEG-1 axis have not yet been examined widely in HCC. Here, we explored the expression of both miR-221 and AEG-1 and their target/associate genes by qRT-PCR and western blot. In addition, the role of the miR-221/AEG-1 axis was studied in the HCC by flow cytometry analysis. The expression level of the AEG-1 did not change in the miR-221 mimic, and miR-221-transfected HCC cells, on the other hand, decreased the miR-221 expression in AEG-1 siRNA-transfected HCC cells. The miR-221/AEG-1 axis silencing induces apoptosis and G2/M phase arrest and inhibits cellular proliferation and angiogenesis by upregulating p57, p53, RB, and PTEN and downregulating LSF, LC3A, Bcl-2, OPN, MMP9, PI3K, and Akt in HCC cells.

Breaking new frontiers: Assessment and re-evaluation of clinical trial design for nutraceuticals.

Despite sophisticated study designs and measurement tools, we have yet to create an innovative space for diet and dietary supplements in the health care system. The path is challenging due to current hierarchies of scientific evidence and regulatory affairs. The role of the randomized, double-blind, placebo-controlled clinical trial (RCT) as a research approach functions well to characterize the benefits and risks of drugs but lacks the sensitivity to capture the efficacy and safety of nutraceuticals. While some facets of RCTs can be relevant and useful when applied to nutraceuticals, other aspects are limiting and potentially misleading when taken in their entirety. A differentiation between guidelines for evidence-based medicine and the evidence required for nutrition spotlight the need to reconceptualize constituents of the RCT and their applicability with relevance to health promotion. This perspective identifies the limitations of the traditional RCT to capture the complexities of nutraceuticals and proposes the N-of-1 as Level 1 evidence better suited for the proof of efficacy of nutraceuticals.

The absence of cellular glucose triggers oncogene AEG-1 that instigates VEGFC in HCC: A possible genetic root cause of angiogenesis.

BACKGROUND AND OBJECTIVE: Astrocyte Elevated Gene-1 (AEG-1) is the master and multi-regulator of the various transcriptional factor primarily regulating chemoresistance, angiogenesis, metastasis, and invasion under the pathological condition, including liver cancer. This study was focused on investigating the process of tumor angiogenesis in liver carcinoma by studying the role of AEG-1 under GD/2DG conditions. METHOD AND RESULTS: The PCR and western blot analysis revealed that glucose depletion (GD) induces the overexpression of AEG-1. Further, it leads to the constant expression of VEGFC through the activation of HIF-1α/CCR7 via the stimulations of PI3K/Akt signaling pathways. GLUT2 is the major transporter of a glucose molecule that is highly participating under GD through the expression of AEG-1 and constantly expresses glucokinase (GCK). The obtained data suggest that AEG-1 act as an angiogenesis and glycolysis regulator by modulating the expression of GCK through HIF-1α and GLUT2. 2-deoxy-D-glucose (2DG) is a glycolysis inhibitor that induces impaired glycolysis and cellular apoptosis by cellular oxidative stress. The administration of 2DG has led to the chemoresistance of AEG-1. CONCLUSION: The total findings of the study judged that disruption of cellular energy metabolism induced by the absence of glucose or the presence of mutant glucose moiety (2DG) promotes the overexpression of AEG-1. The GD/2DG activates the VEGFC by inducing the HIF-1α and CCR7. Moreover, AEG-1 induces the expression of OPN, which regulates metastasis, angiogenesis, and actively participates in protective autophagy by promoting LC3 a/b.

Circulatory microRNA expression profile for coronary artery calcification in chronic kidney disease patients.

BACKGROUND & AIM: Coronary artery disease (CAD) is the primary cause of mortality in patients with end stage renal disease (ESRD). MicroRNA profiling is proven as a powerful tool in the diagnosis of any disease at the molecular level. Hence, the present study aimed to profile the microRNA expression for CAD especially coronary artery calcification in CKD patients. MATERIALS AND METHODS: Two hundread patients with CKD stages 3 to 5 without dialysis and healthy controls were included in this study. All two hundred patients underwent 1024 multi sliceardiac computed tomography (CT) scan for calcium scoring. The calcium scoring more than 100 have been included in the study. We performed miRNA microarray analysis from serum samples of seven high calcium scored with CKD patients and one control patients. RESULTS: Seven patients have observed circulating miRNAs has significantly upregulated and downregulated when compared with control patients. mir21, mir 67, mir 390, mir 56, mir 250, mir 65 and mir 13 were up regulated and mir235, mir256, mir226, mir207, mir255, mir193 were downregulated. There was no significant difference in left ventricle function. CONCLUSION: 13 microRNAs play a potential role in coronary artery calcification in CKD patients.

Corrigendum: Dysregulation of miR-375/AEG-1 Axis by Human Papillomavirus 16/18-E6/E7 Promotes Cellular Proliferation, Migration, and Invasion in Cervical Cancer.

[This corrects the article DOI: 10.3389/fonc.2019.00847.].

Enhancing the fresh water produced from inclined cover stepped absorber solar still using wick and energy storage materials.

Renewable energy-based desalination (RED) technique is gaining more importance over the desalination techniques as it appeared to be a promising technique towards low-cost desalination for sustainable growth as the energy demand towards other developments is continuously increasing. This study aims to incorporate energy storage materials and wick materials in the inclined solar to improve the fresh water produced. In this work, the performance of inclined solar still using coconut coir disk and energy storage material is analyzed experimentally. Characterization results showed that the porosity, absorbency, capillary rise, and heat transfer coefficient of 1-year dried coconut coir disk were found as 73.25%, 2 s, 10 mm/h, and 37.21 W/m2K, respectively, which is higher as compared with that of other coconut coir disks. The experimental results on the performance showed that total distillate from novel inclined solar still with hybrid techniques (energy storage materials and wick materials) were recorded as 3645, 4080, 4570, and 4890 ml for 3 months, 6 months, 9 months, and 1 year, respectively. While the total distillate outputs of an inclined solar still with only wick materials were recorded as 2560, 2670, 2930, and 3390 ml for 3 months, 6 months, 9 months, and 1-year coconut coir disk wick materials. The novel hybrid techniques used in the inclined solar still with energy storage materials enhanced the yield from 82.25 to 144.5% than the conventional solar still, whereas the inclined solar still with only wick materials enhanced the yield from 28 to 69.5% than the conventional solar still.

Extraction of microplastics from commonly used sea salts in India and their toxicological evaluation.

Microplastics (MPs) are one of the marine debris, accumulated in the ocean as a result of the successive breakdown of a large piece of plastics over several years. MPs are about less than 5 mM, have a detrimental impact on marine organisms/products (seafood/sea salts) and therefore they are considered as a global environmental pollutant. The occurrence and impact of MPs in commercial sea salts that are consumed by humans are not well studied so far. In the present study, we attempted to characterize and evaluate the in vitro toxicity of isolated MPs. Here, we have used ten brands of commercial sea salts of different origins for the identification and characterization of MPs. The average abundance of MPs in all commercial brands is < 700 MP/kg and the particle size range between 5.2 mM and 3.8 µM. The most common types of MPs were identified as fragments, fibers, and pellets. By Fourier-Transform infrared spectroscopy (FT-IR), it was found that the MPs in abundance were made of cellophane (CP), polystyrene (PR), polyamide (PA) and polyarylether (PAR). Further, in vitro toxicity assessment revealed that HEK-293 cells get detached upon treatment with MPs (MIC-75 µg mL-1) Consequently, the AO/EB dual staining confirmed that the induction and rate of apoptosis were comparatively higher in microplastic treated HEK-293 cells. Taken together, the MPs identified are the origin of anthropogenic derivatives and they exert a lethal effect on human cells, which might be associated with health risk complications in human beings.

Erratum to "Changing the tone of clinical study design in the cannabis industry".

[This corrects the article on p. 4 in vol. 11, PMID: 32104589.].

Efficacy of Lactobacillus paracasei HA-196 and Bifidobacterium longum R0175 in Alleviating Symptoms of Irritable Bowel Syndrome (IBS): A Randomized, Placebo-Controlled Study.

Specific probiotic strains can alleviate the gastrointestinal (GI) symptoms and psychiatric comorbidities of irritable bowel syndrome (IBS). In this randomized, double-blind, placebo-controlled study, the efficacy of Lactobacillus paracasei HA-196 (L. paracasei) and Bifidobacterium longum R0175 (B. longum) in reducing the GI and psychological symptoms of IBS was evaluated in 251 adults with either constipation (IBS-C), diarrhea (IBS-D), or mixed-pattern (IBS-M). Following a 2-week run-in period, participants were randomized to one of three interventions: L. paracasei (n = 84), B. longum (n = 83) or placebo (n = 81). IBS symptoms, stool frequency and consistency and quality of life were assessed by questionnaires. The differences from baseline in the severity of IBS symptoms at 4 and 8 weeks were similar between groups. Participants in this study were classified, after randomization, into subtypes according to Rome III. Within the L. paracasei group, complete spontaneous and spontaneous bowel movement frequency increased in participants with IBS-C (n = 10) after 8 weeks of supplementation (both p < 0.05) and decreased in participants with IBS-D (n = 10, p = 0.013). Both L. paracasei and B. longum supplementation improved the quality of life in emotional well-being and social functioning compared with baseline (all p < 0.05). In conclusion, L. paracasei and B. longum may reduce GI symptom severity and improve the psychological well-being of individuals with certain IBS subtypes.

Changing the Tone of Clinical Study Design in the Cannabis Industry.

Cannabis (also known as marijuana) is the most frequently used psychoactive substance globally. Cannabis exerts therapeutic functions for many indications and has vast potential as a health and wellness product. Advances in our understanding of the composition and pharmacological properties of cannabis have revealed interactions between cannabis, an individuals' circadian rhythms and and their endocannabinoid signaling. Exogenously administered cannabinoids can bidirectionally entrain central and peripheral clocks that comprise circadian rhythms, and malfunctions in the endocannabinoid system are reported to impact neurological processes. Therefore, it is necessary to account for the circadian rhythm when designing clinical trials examining the pharmacological properties of cannabis-based products for health and wellness to limit its potential confounding impact on results. Consideration of the entrainment capabilities of the endocannabinoid system is warranted when designing clinical trials.

Biomimetic gold nanoparticles for its cytotoxicity and biocompatibility evidenced by fluorescence-based assays in cancer (MDA-MB-231) and non-cancerous (HEK-293) cells.

Biomimetic gold nanoparticles of biological origin have created a significant impact on the field of biomedicine due to the great expectations of its applications. Because of this, the influences of biomimetic gold nanoparticles have been immensely studied, targeting various cancer cells. However, the impact of biomimetic gold nanoparticles against normal non-cancerous cells is scanty, which impose several limitations in their utility. Taking this as a challenge, we in this study report the biomimetic gold nanoparticles from marine seaweed Gelidium pusillum (G. pusillum) to evaluate its cytotoxic and biocompatible ability evidenced by fluorescence-based assays in cultured cells. The gold nanoparticles obtained in the study were spherical shaped with a mean diameter of 12 ± 4.2 nm. The seaweed extract plays a crucial role in stabilizing the gold nanoparticles to avoid aggregation and coalescence. At an IC50 concentration of 43.09 ± 1.6 µgmL-1, the biomimetic gold nanoparticles were found to be toxic to cancerous cells (MDA-MB-231). Whereas, biomimetic gold nanoparticles exhibit significant biocompatibility with human embryonic kidney cells even at a higher concentration of 150 µgmL-1. The morphological based fluorescence assays confirmed the ability of biomimetic gold nanoparticles in inducing apoptosis and thereby kills cancer cells. Altogether, the gold nanoparticles were safe to normal cells and did not show a significant impact. Hence, the novel biomimetic gold nanoparticles hold potential as multifaceted agent and can further be taken up to various biomedical applications.