MicroRNAs: A Neoteric Approach to Understand Pathogenesis, Diagnose, and Treat Myocardial Infarction.

ABSTRACT: Myocardial infarction is a substantial contributor to ischemic heart diseases, affecting a large number of people leading to fatal conditions worldwide. MicroRNAs (miRNAs) are explicitly emerging as excellent modulators of pathways involved in maintaining cardiomyocyte survival, repair, and regeneration. Altered expression of genes in cardiomyocytes postinfarction can lead to the disordered state of the myocardium, such as cardiac hypertrophy, ischemia-reperfusion injury, left ventricular remodeling, and cardiac fibrosis. Therapeutic targeting of miRNAs in cardiomyocytes can potentially reverse the adverse effects in the heart postinfarction. This review aims to understand the role of several miRNAs involved in the regeneration and repair of cardiomyocytes postmyocardial infarction and presents comprehensive information on the subject.

Gene expression is influenced due to 'nano' and 'ionic' copper in pre-formed Pseudomonas aeruginosa biofilms.

Today, researchers across the globe suggest the use of antimicrobial coatings containing copper nanoparticles (CuNPs) complementing the traditional protocols to prevent hospital-acquired infections (HAIs). Since Pseudomonas aeruginosa is one of the commonest opportunistic pathogens, we assessed the anti-biofilm activity of CuNPs in P. aeruginosa MTCC 3541 and compared it with Cu2+ (copper sulphate) since the latter continues to be used as an antimicrobial-of-choice in food industries, agriculture and water treatment. In this study, we synthesized and characterized stable poly-acrylic acid (PAA) coated CuNPs with a size of 66-150 nm and zeta potential -13 mV. Pseudomonas aeruginosa MTCC 3541 biofilms were highly resistant to both CuNPs and Cu2+ (minimum biofilm inhibitory concentration, MBIC 300 and >600 µg/mL respectively). Scanning electron microscopy revealed alterations in cell morphology upon treatment with CuNPs. A closer analysis of the biofilm-specific gene expression (qRT-PCR) revealed that CuNPs downregulated the genes involved in biofilm matrix formation, motility, efflux, membrane lipoprotein synthesis and DNA replication. Both, CuNPs and Cu2+ up regulated copper resistance and biofilm dispersion genes. Copper did not affect the bacterial communication system as evidenced by downregulation of the negative regulator of quorum sensing. The gene expression analysis reveals multiple cellular targets for CuNPs and ionic Cu. The present study highlights the fact that CuNPs affect the membrane functions adversely damaging the cell surface. In pre-formed biofilms, CuNPs were more toxic and displayed distinct responses attributable due to 'nano' and 'ionic' copper. Our findings thus support the use of CuNPs for curbing HAIs.

Inhibition of ß-Amyloid Aggregation through a Designed ß-Hairpin Peptide.

Designing peptide-based drugs to target the ß-sheet-rich toxic intermediates during the aggregation of amyloid-ß 1-42 (Aß1-42) has been a major challenge. In general, ß-sheet breaker peptides (BSBPs) are designed to complement the enthalpic interactions with the aggregating protein, and entropic effects are usually ignored. Here, we have developed a conformationally constrained cyclic BSBP by the use of an unnatural amino acid and a disulfide bond. We show that our peptide strongly inhibits the aggregation of Aß1-42 in a concentration-dependent manner. It stabilizes the random coil conformation of Aß1-42 monomers and inhibits the secondary structural transition to a ß-sheet-rich conformation which allows Aß1-42 to oligomerize in an ordered assembly during its aggregation. Our cyclic peptide also rescues the toxicity of soluble aggregates of Aß1-42 toward neuronal cells. However, it significantly loses its potency in the conformationally relaxed acyclic form. It appears that limiting the loss of conformational entropy of the BSBP ligand can play a very important role in the attainment of conformations for precise and tight binding, making them a potent inhibitor for Aß1-42 amyloidosis.

Lateral flow assay for rapid detection of white spot syndrome virus (WSSV) using a phage-displayed peptide as bio-recognition probe.

White spot disease caused by the white spot syndrome virus (WSSV) has a major socio-economic impact on shrimp farming in India. It has been realized that a field-usable diagnostic capable of rapid detection of WSSV can prevent huge economic losses in disease outbreaks. In this work, we explored the possibility of using a peptide as bio-recognition probe in a field-usable device for the detection of WSSV from infected shrimps and prawns. A commercially available random phage-display library was screened against rVP28 (a major structural protein of WSSV, expressed as a recombinant protein in Escherichia coli). A bacteriophage clone VP28-4L was obtained, and its binding to purified rVP28 protein as well as WSSV from infected shrimp Litopaeneus vannamei tissue was confirmed by ELISA and western blot. The apparent equilibrium dissociation constant (Kd,app) was calculated to be 810 nM. VP28-4L did not show cross-reactivity with any other shrimp viruses. A 12-mer peptide (pep28, with the sequence 'TFQAFDLSPFPS') displayed on the VP28-4L was synthesized, and its diagnostic potential was evaluated in a lateral flow assay (LFA). Visual detection of WSSV could be achieved using biotinylated-pep28 and streptavidin-conjugated gold nanoparticles. In LFA, 12.5 µg/mL of the virus could be detected from L. vannamei gill tissue homogenate within 20 min. Pep28 thus becomes an attractive candidate in bio-recognition of WSSV in field-usable diagnostic platforms benefitting the aquaculture sector.

Anti-diabetic activity and safety assessment of Ayurvedic medicine, Jasada bhasma (zinc ash) in rats.

Jasada bhasma (zinc ash) is an extensively used Ayurvedic medicine for treating diabetes mellitus. The present communication presents yet unavailable comprehensive scientific data on its physico-chemical nature vis-a-vis anti-diabetic activity and toxicity profile.Zinc ash prepared by traditional method was found to consist of 200-500 nm sized particles, predominantly zinc oxide with hexagonal wurtzite crystal structure. The effective dose range of zinc ash in oral glucose tolerance tests performed using normoglycemic Wistar rats was found to be 3-30 mg/kg. Subsequently anti-diabetic activity was assessed in streptozotocin induced type 1 and type 2 diabetic rats. Four weeks treatment with zinc ash (1, 3, 10 mg/kg) resulted in improved glucose tolerance (16-19%), lowered blood glucose levels (20-33%) and reduced serum insulin levels (27-32%). Systemic absorption was assessed by single dose pharmacokinetic study where serum zinc levels were found to be elevated (3.5 folds) after oral administration of zinc ash. Acute and sub-acute toxicity tests demonstrated safety of zinc ash up to 300 mg/kg doseie. 100 times the efficacy dose in rats. These findings, the first of their kind, provide concrete scientific evidence that justifies usage of zinc ash in diabetes treatment.

Nucleolin aptamer conjugated MSNPs-PLR-PEG multifunctional nanoconstructs for targeted co-delivery of anticancer drug and siRNA to counter drug resistance in TNBC.

The emergence of drug resistance in cancer cells is among the major challenges for treating cancer. In the last few years, the co-delivery of drug and siRNA has shown promising results against drug-resistant cancers. In the present study, we developed mesoporous silica-based multifunctional nanocarrier for co-delivery against drug-resistant triple-negative breast cancer (TNBC) cells. We synthesized the nanocarrier by modifying mesoporous silica nanoparticles with poly-L-arginine, polyethylene glycol and AS1411 aptamer to impart siRNA binding ability, biocompatibility, and cancer cell specificity, respectively. We optimized the loading of doxorubicin (DOX) within the developed nanocarrier to avoid interference with siRNA binding. We ascertained the target specificity by performing a receptor blockade assay during cellular uptake studies. The cytotoxic efficacy of DOX and siRNA co-delivered using the developed nanocarrier was assessed using DOX-resistant MDA-MB-231 TNBC cells. The nanocarrier exhibited >10-fold and 40-fold reduction in the IC50 values of DOX due to co-delivery with BCl-xL and BCL-2 siRNA, respectively. The results were further validated using a 3-D in vitro cell culture system. This study demonstrates that the targeted co-delivery of drug and siRNA has a strong potential to overcome drug resistance in TNBC cells.

Targeted silencing of the MCL-1 gene using multi-layered dendrimer-based nanoconstructs achieves efficient tumor regression in xenografted mice models.

The setback in the practical clinical use of RNA interference (RNAi)-based cancer treatment stems from the lack of targeted small interfering RNA (siRNA) delivery. Here, we show that luteinizing hormone-releasing hormone(LHRH) analog-tethered multi-layered polyamidoamine (PAMAM) nanoconstructs silence the anti-apoptotic MCL-1 gene in LHRH receptor overexpressing human breast (MCF-7) and prostate cancer (LNCaP) cells with 70.91 % and 74.10 % efficiency, respectively. These results were confirmed by RT-PCR. The Acridine orange/Ethidium bromide (AO/EB) dual staining revealed that the silencing of MCL-1 induced apoptosis in both the cell lines. In vivo tumor regression studies performed using MCF-7 and LNCaP xenografted severe combined immunodeficiency(SCID) mice demonstrated highly improved tumor regression in groups treated with targeted nanoconstructs complexed with MCL-1 siRNA (T + siMCL-1) compared to the other treatment groups. The quantitative RT-PCR results of tumor tissues demonstrated significant MCL-1 gene silencing, i.e., 73.76 % and 92.63 % in breast and prostate tumors, respectively, after T + siMCL-1 treatment. Reduction in MCL-1 protein expression as assessed by immunohistochemistry further confirmed these results. Furthermore, the caspase 3/7 assay demonstrated apoptosis in the MCL-1 silenced tissues. The study strongly suggests that targeted delivery of siRNAs using multi-layered dendrimer nanostructures could be an effective therapy for LHRH overexpressing cancers.

Nanotoxicology and in vitro studies: the need of the hour.

Nanotechnology is considered as one of the key technologies of the 21st century and promises revolution in our world. Objects at nano scale, take on novel properties and functions that differ markedly from those seen in the corresponding bulk counterpart primarily because of their small size and large surface area. Studies have revealed that the same properties that make nanoparticles so unique could also be responsible for their potential toxicity. Nanotechnology is rapidly advancing, with more than 1000 nanoproducts already on the market. Considering the fact that intended as well as unintended exposure to nanomaterials is increasing and presently no clear regulatory guideline(s) on the testing/evaluation of nanoparticulate materials are available, the in vitro toxicological studies become extremely relevant and important. This review presents a summary of nanotoxicology and a concise account of the in vitro toxicity data on nanomaterials. For nanomaterials to move into the applications arena, it is important that nanotoxicology research uncovers and understands how these multiple factors influence their toxicity so that the ensuing undesirable effects can be avoided.

Hyperthermia and doxorubicin release by Fol-LSMO nanoparticles induce apoptosis and autophagy in breast cancer cells.

Background: Studies on the anticancer effects of lanthanum strontium manganese oxide (LSMO) nanoparticles (NPs)-mediated hyperthermia at cellular and molecular levels are scarce. Materials & methods: LSMO NPs conjugated with folic acid (Fol-LSMO NPs) were synthesized, followed by doxorubicin-loading (DoxFol-LSMO NPs), and their effects on breast cancer cells were investigated. Results: Hyperthermia (45°C) and combination treatments exhibited the highest (∼95%) anticancer activity with increased oxidative stress. The involvement of intrinsic mitochondria-mediated apoptotic pathway and induction of autophagy was noted. Cellular and molecular evidence confirmed the crosstalk between apoptosis and autophagy, involving Beclin1, Bcl2 and Caspase-3 genes with free reactive oxygen species presence. Conclusion: The study confirmed hyperthermia and doxorubicin release by Fol-LSMO NPs induces apoptosis and autophagy in breast cancer cells.

An Indigenous, Field-Deployable, Lateral Flow Immunochromatographic Assay Rapidly Detects Infectious Myonecrosis in Shrimp, Litopenaeus vannamei.

Shrimp farming is an important socioeconomic activity worldwide. Infectious myonecrosis virus (IMNV) is an important shrimp virus responsible for significant mortality (up to 70%) in Litopenaeus vannamei. We produced recombinant capsid protein (r-IMNV31) and obtained a highly specific antibody, anti-r-IMNV31, which was used in WOAH-approved ELISA and Western blot to detect IMNV. Further, anti-r-IMNV31 was employed in an indigenously developed lateral flow immunoassay (LFA) with gold nanoparticles as a visual label. Using LFA, IMNV could be detected rapidly (20 min) from tissue homogenate with high specificity, reproducibility, and sensitivity (LOD = 103 viral particles). LFA was validated with "gold standard" qRT-PCR using 60 samples with high sensitivity (100%), specificity (86%). A Cohen's kappa coefficient of 0.86 suggested "good agreement" between LFA and qRT-PCR. With a shelf-life of ~ 1 year at ambient temperature, the use of LFA in the on-site detection of IMNV by shrimp farmers will be a reality.

miRNA transfection via poly(amidoamine)-based delivery vector prevents hypoxia/reperfusion-induced cardiomyocyte apoptosis.

Aim: Myocardial infarction is a tissue injury that leads to apoptosis of cardiomyocytes. This can be prevented by using miRNAs, but its delivery to cardiomyocytes is a major hurdle. We aimed to deliver miRNAs using poly(amidoamine)-histidine (PAMAM-His) nanocarriers to prevent apoptosis. Materials & methods: The PAMAM-His nanoparticles were synthesized and assessed for their transfection efficiency of miRNAs to prevent apoptosis in hypoxia/reperfusion-induced H9c2 as well as primary cultured cardiomyocytes. Results & conclusion: miRNAs-nanoparticle complexes exerted a significant antiapoptotic effect on the H9c2 and primary rat ventricular cardiomyocytes. Enhanced expression of antiapoptotic genes and decreased expression of proapoptotic genes were observed. PAMAM-His nanoparticles effectively delivered miRNAs to the cardiomyocytes and prevented the hypoxia/reperfusion-induced apoptosis critical in myocardial infarctions.

Non-nuke HIV-1 inhibitor shuttled by mesoporous silica nanoparticles effectively slows down HIV-1 replication in infected human cells.

The objectives of this study were to reduce the cytotoxic effect of nevirapine (NVP) and to enhance its anti-HIV efficacy through mesoporous silica nanoparticles (MSNPs) mediated delivery. MSNPs were synthesized and characterized by various techniques. Confocal microscopy and flow cytometry results exhibited efficient uptake of FITC-conjugated MSNPs in TZM-bl cells. The NVP was loaded within MSNPs, and its anti-HIV1 efficacy was assessed on HIV1 (R5 and X4 variants) infected TZM-bl cells and further confirmed on peripheral blood mononuclear cells (PBMCs). The in vitro assessment of the anti-HIV1 potential of NVP and NVP-MSNPs in HIV1 infected TZM-bl cells and PBMCs showed increased efficacy of NVP upon loading within MSNPs with significant increase in therapeutic index. The increased efficacy against HIV1 was accompanied by reduced cytotoxicity to TZM-bl cells and PBMCs. Further, reverse transcriptase (RT) assay confirmed the inhibitory effect on RTase, which is a key enzyme in HIV-1 replication. The present study showed that entrapment of NVP within MSNPs led to an increased efficacy with reduced cytotoxic effect resulting in the enhanced therapeutic index (TI).

Tumor suppressor protein SMAR1 modulates the roughness of cell surface: combined AFM and SEM study.

BACKGROUND: Imaging tools such as scanning electron microscope (SEM) and atomic force microscope (AFM) can be used to produce high-resolution topographic images of biomedical specimens and hence are well suited for imaging alterations in cell morphology. We have studied the correlation of SMAR1 expression with cell surface smoothness in cell lines as well as in different grades of human breast cancer and mouse tumor sections. METHODS: We validated knockdown and overexpression of SMAR1 using RT-PCR as well as Western blotting in human embryonic kidney (HEK) 293, human breast cancer (MCF-7) and mouse melanoma (B16F1) cell lines. The samples were then processed for cell surface roughness studies using atomic force microscopy (AFM) and scanning electron microscopy (SEM). The same samples were used for microarray analysis as well. Tumors sections from control and SMAR1 treated mice as well as tissues sections from different grades of human breast cancer on poly L-lysine coated slides were used for AFM and SEM studies. RESULTS: Tumor sections from mice injected with melanoma cells showed pronounced surface roughness. In contrast, tumor sections obtained from nude mice that were first injected with melanoma cells followed by repeated injections of SMAR1-P44 peptide, exhibited relatively smoother surface profile. Interestingly, human breast cancer tissue sections that showed reduced SMAR1 expression exhibited increased surface roughness compared to the adjacent normal breast tissue. Our AFM data establishes that treatment of cells with SMAR1-P44 results into increase in cytoskeletal volume that is supported by comparative gene expression data showing an increase in the expression of specific cytoskeletal proteins compared to the control cells. Altogether, these findings indicate that tumor suppressor function of SMAR1 might be exhibited through smoothening of cell surface by regulating expression of cell surface proteins. CONCLUSION: Tumor suppressor protein SMAR1 might be used as a phenotypic differentiation marker between cancerous and non-cancerous cells.

Smart triblock dendritic unimolecular micelles as pioneering nanomaterials: Advancement pertaining to architecture and biomedical applications.

Recent interest in triblock dendritic unimolecular micelles has opened a new spectrum for its ubiquitous application in biomedical sciences specially drug delivery. Unimolecular dendritic micelles have brought significant attention due to their high encapsulation efficiency, high-functionality, and site specific confinement capabilities. During the last decade, the number of publications in this field has increased drastically, reinforced by the fact that several clinical trials are underway using micelles for drug delivery. This review unveils the most recent advancement on the synthesis and applications of cutting-edge unimolecular micelles using dendritic and star-shaped molecules emphasizing on triblock copolymers. The major biomedical applications covered in this manuscript are drug/gene/bio-macromolecules delivery to the site of interest, as contrast agents in bio-imaging, and cancer targeted theranostics using stimuli-responsive mechanism.

A robust pH-sensitive unimolecular dendritic nanocarrier that enables targeted anti-cancer drug delivery via GLUT transporters.

This study explores the potential of dendritic unimolecular nanoconstruct, PAMAM-Tryptophan-(N-acetylglucosamine) [PTN] as anti-cancer drug delivery system. The PAMAM dendrimers were modified with L-tryptophan and N-acetyl glucosamine (NAG) for higher drug loading and to utilize GLUT transporters, respectively. The nanocarriers were characterized by 1H NMR, DSC, and dynamic light scattering. Effect of doxorubicin (DOX)- loaded PTN was studied on MDA-MB-231 and HepG2 cells by cell viability assay. Further flow cytometry analysis was carried out to assess apoptosis. Pre-treatment with NAG was carried out to keep GLUT transporters continuously engaged and to determine GLUT targeting. Confocal microscopy demonstrated significantly higher uptake of FITC tagged PTN than PAMAM. DOX-loaded PTN demonstrated pH-sensitive drug release with significant (P < 0.001) higher cytotoxicity against breast cancer cells than PAMAM. The percentage viability after 48 h was found to be 5.0 ± 2.32, 18.3 ± 2.91 and 5.9 ± 0.55% for free DOX, PAMAM-DOX, and PTN-DOX, respectively in MDA-MB-231 cells. A similar profile was observed for HepG2 cells. Further, flow cytometry analysis confirmed that the cell death mode was apoptosis. Pre-treatment with NAG during cell viability assay and flow cytometry evidenced GLUT targeting. Taken together, conjugating tryptophan to parent dendrimer could significantly enhance cargo loading capacity and binding NAG could be an attractive therapeutic approach for GLUT transporters mediated delivery of anticancer drugs.

Mesoporous silica nanoparticles as cutting-edge theranostics: Advancement from merely a carrier to tailor-made smart delivery platform.

Large surface area, uniform and tunable pore size, high pore volume and low mass density- such attractive features of Mesoporous silica nanoparticles (MSNPs) have compelled researchers to explore the biomedical potential of this nano-material. Recently gained interest in MSNPs have been due to their tremendous potential in cancer therapy and imaging. Last several years have witnessed a rapid development in engineering functionalized MSNPs with various types of functional groups integrated into the system for imaging and therapeutic applications. Although their potential for drug delivery application has been studied since the year 2000, still a major challenge is to improve drug loading capacity and in vivo targeting with minimal side-effects to major organs. In this review article, the recent development of MSNPs as a therapeutic and diagnostic platform has been detailed out with emphasis on drug and bio-macromolecule delivery/co-delivery, bio-imaging and detoxification.

Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells.

BACKGROUND: Considering the increase in cancer cases and number of deaths per year worldwide, development of potential therapeutics is imperative. Mesoporous silica nanoparticles (MSNPs) are among the potential nanocarriers having unique properties for drug delivery. Doxorubicin (DOX), being the most commonly used drug, can be efficiently delivered to gonadotropin-releasing hormone (GnRH)-overexpressing cancer cells using functionalized MSNPs. AIM: We report the development of decapeptide-conjugated MSNPs loaded with DOX for the targeted drug delivery in breast and prostate cancer cells. MATERIALS AND METHODS: MSNPs were synthesized and subsequently functionalized with an analog of GnRH by using a heterobifunctional polyethylene glycol as a linker. These targeted MSNPs were then characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. An anticancer drug DOX was loaded and then characterized for drug loading. DOX-loaded nanocarriers were then studied for their cellular uptake using confocal microscopy. The cytotoxicity of DOX-loaded targeted MSNPs and DOX-loaded bare MSNPs was studied by performing MTT assay on MCF-7 (breast cancer) and LNCaP (prostate cancer) cells. Further, acridine orange/ethidium bromide staining, as well as flow cytometry, was performed to confirm the apoptotic mode of cancer cell death. RESULTS: MSNPs were conjugated with polyethylene glycol as well as an agonist of GnRH and subsequently loaded with DOX. These targeted and bare MSNPs showed excellent porous structure and loading of DOX. Further, higher uptake of DOX-loaded targeted MSNPs was observed as compared to DOX-loaded bare MSNPs in GnRH-overexpressing breast (MCF-7) and prostate (LNCaP) cancer cells. The targeted MSNPs also showed significantly higher (P<0.001) cytotoxicity than DOX-loaded bare MSNPs at different time points. After 48 hours of treatment, the IC50 value for DOX-loaded targeted MSNPs was found to be 0.44 and 0.43 µM in MCF-7 and LNCaP cells, respectively. Acridine orange/ethidium bromide staining and flow cytometry analysis further confirmed the pathway of cell death through apoptosis. CONCLUSION: This study suggests GnRH analog-conjugated targeted MSNPs can be the suitable and promising approach for targeted drug delivery in all hormone-dependent cancer cells.

Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding domain) controls breast tumor in mice model.

AIM: To investigate anticancer activity of the DNA binding domain of SMAR1 (His 5) in vitro and in vivo. MATERIALS & METHODS: His 5 was conjugated to hydrothermally synthesized carbon nanospheres (CNs). Anticancer activity of CNs-His 5 was evaluated in vitro and in vivo. RESULTS: CNs- His 5 significantly reduced cyclin D1 levels in MDA-MB-231 cells. Tumor bearing Balb/c mice injected with CNs-His 5 showed approximately 62% tumor regression and significantly reduced 18FDG uptake. Caspases assay and IHC staining confirmed tumor growth inhibition, which could be attributed to apoptotic, antiproliferative and antiangiogenic activities of His 5. CONCLUSION: DNA binding domain of the SMAR1 protein (His 5) has potent anticancer activity and its CNs mediated delivery could control breast tumor in mice model.

Zinc use efficiency is enhanced in wheat through nanofertilization.

Ferti-fortification of wheat with zinc, an essential micronutrient is one of the strategies for combating 'hidden hunger' in a large proportion of people all over the world. During fertilization, application of large quantities of micronutrients often results in nutrient wastage and subsequent environmental pollution. Here, we report zinc complexed chitosan nanoparticles (Zn-CNP) for ferti-fortification of durum wheat in field-scale experiments. The efficacy of Zn-CNP was assessed vis-à-vis conventionally applied ZnSO4 (0.2%; 400 mgL-1 zinc) in two durum wheat genotypes (MACS 3125, an indigenous high yielding genotype and UC 1114, a genotype containing the Gpc-B1gene). The observed grain zinc enrichment using Zn-CNP nanocarrier (~36%) and conventional ZnSO4 (~50%) were comparable, despite 10 folds less zinc (40 mgL-1) used in the former. Nanofertilizer application increased grain zinc content without affecting grain yield, protein content, spikelets per spike, thousand kernel weight, etc. Grain zinc enrichment observed in the four-year field trials on plots with varying soil zinc content was consistent, proving the utility of Zn-CNP as a novel nanofertilizer which enhanced fertilizer use efficiency. Our work describes a new paradigm in micronutrient fortification, viz. 'use nanofertilizers at the right place, right time and in right doses'.

Applications of cobalt ferrite nanoparticles in biomedical nanotechnology.

Magnetic nanoparticles (MNPs) are very attractive especially for biomedical applications, among which, iron oxide nanoparticles have received substantial attention in the past decade due to the elemental composition that makes them biocompatible and degradable. However recently, other magnetic nanomaterials such as spinel ferrites that can provide improved magnetic properties such as coercivity and anisotropy without compromising on inherent advantages of iron oxide nanoparticles are being researched for better applicability of MNPs. Among various spinel ferrites, cobalt ferrite (CoFe2O4) nanoparticles (NPs) are one of the most explored MNPs. Therefore, the intention of this article is to provide a comprehensive review of CoFe2O4 NPs and their inherent properties that make them exceptional candidates, different synthesis methods that influence their properties, and applications of CoFe2O4 NPs and their relevant applications that have been considered in biotechnology and bioengineering.