Biosynthesized silver nanoparticles prevent bacterial infection in chicken egg model and mitigate biofilm formation on medical catheters.

Investigating the application of innovative antimicrobial surface coatings on medical devices is an important field of research. Many of these coatings have significant drawbacks, including biocompatibility, coating stability and the inability to effectively combat multiple drug-resistant bacteria. In this research, we developed an antibiofilm surface coating for medical catheters using biosynthesized silver nanoparticles (b-Cs-AgNPs) developed using leaves extract of Calliandra surinamensis. Various characterization techniques were employed to thoroughly characterize the synthesized b-Cs-AgNPs and c-AgNPs. b-Cs-AgNPs were compatible with human normal kidney cells and chicken embryos. It did not trigger any skin inflammatory response in in vivo rat model. b-Cs-AgNPs demonstrated potent zone of inhibition of 19.09 mm when subjected to the disc diffusion method in E. coli confirming strong antibacterial property. Different anti-bacterial assays including liquid growth curve, colony counting assay, biofilm formation assay supported the potent antimicrobial efficacy of b-Cs-AgNPs alone and when coated to medical grade catheters. Mechanistic studies reveal the presence of ferulic acid, that was important for the synthesis of b-AgNPs along with enhanced antibacterial effects of b-Cs-AgNPs compared to c-AgNPs, supported by molecular docking analysis. These results together demonstrated the effective role b-Cs-AgNPs in combating infections and mitigating biofilm formations, highlighting their need for further study in the field of biomedical applications.

Celecoxib potentiates antibiotic uptake by altering membrane potential and permeability in Staphylococcus aureus.

BACKGROUND: We have shown previously that celecoxib enhances the antibacterial effect of antibiotics and has sensitized drug-resistant bacteria to antibiotics at low concentrations using in vitro and in vivo model systems and also using clinically isolated ESKAPE pathogens. OBJECTIVES: To identify the mechanism of action of celecoxib in potentiating the effect of antibiotics on bacteria. METHODS: Toxicogenomic expression analysis of Staphylococcus aureus in the presence or absence of ampicillin, celecoxib or both was carried out by microarray followed by validation of microarray results by flow cytometry and real-time PCR analysis, cocrystal development and analysis. RESULTS: The RNA expression map clearly indicated a change in the global transcriptome of S. aureus in the presence of cells treated with ampicillin alone, which was similar to that of celecoxib-treated cells in co-treated cells. Several essential, non-essential and virulence genes such as α-haemolysin (HLA), enterotoxins and ß-lactamase were differentially regulated in co-treated cells. Further detailed analysis of the expression data indicated that the ion transporters and enzymes of the lipid biosynthesis pathway were down-regulated in co-treated cells leading to decreased membrane permeability and membrane potential. Cocrystal studies using Powder-X-Ray Diffraction (PXRD) and differential scanning calorimetry (DSC) indicated interactions between celecoxib and ampicillin, which might help in the entry of antibiotics. CONCLUSIONS: Although further studies are warranted, here we report that celecoxib alters membrane potential and permeability, specifically by affecting the Na+/K+ ion transporter, and thereby increases the uptake of ampicillin by S. aureus.

Nanoporous capsules of block co-polymers of [(MeO-PEG-NH)-b-(L-GluA)]-PCL for the controlled release of anticancer drugs for therapeutic applications.

Herein, new nanoporous capsules of the block co-polymers of MeO-PEG-NH-(L-GluA)10 and polycaprolactone (PCL) have been synthesized through a surfactant-free cost-effective self-assembled soft-templating approach for the controlled release of drugs and for therapeutic applications. The nanoporous polymer capsules are designed to be biocompatible and are capable of encapsulating anticancer drugs (e.g., doxorubicin hydrochloride (DOX) and imatinib mesylate (ITM)) with a high extent (∼279 and ∼480 ng µg(-1), respectively). We have developed a nanoformulation of porous MeO-PEG-NH-(L-GluA)10-PCL capsules with DOX and ITM. The porous polymer nanoformulations have been programmed in terms of the release of anticancer drugs with a desired dose to treat the leukemia (K562) and human carcinoma cells (HepG2) in vitro and show promising IC50 values with a very high mortality of cancer cells (up to ∼96.6%). Our nanoformulation arrests the cell divisions due to 'cellular scenescence' and kills the cancer cells specifically. The present findings could enrich the effectiveness of idiosyncratic nanoporous polymer capsules for use in various other nanomedicinal and biomedical applications, such as for killing cancer cells, immune therapy, and gene delivery.

Designing idiosyncratic hmPCL-siRNA nanoformulated capsules for silencing and cancer therapy.

In this work, we have designed a siRNA-nanoformulation with mesoporous polycaprolactone (hmPCL) for silencing and cancer therapy. Average hollow core size of hmPCL nanocapsules used for nanoformulation is ~180 nm with shell thickness of 10-20 nm and mesopore size of ~5-10nm in diameter. Idiosyncratic capsules are biocompatible which has been confirmed with normal lymphocyte, K562 leukaemia cancer cells and on HepG2/EGFP cancer cells. In 1mg of hmPCL capsules up to 400 ng of siRNA can be loaded. This nanoformulation enables to tune the dose dependent delivery up to ~93.25% (373 ng) siRNA during therapy. hmPCL-siRNA nanoformulation mediated siRNA transfection on HepG2 cancer cells has been investigated and exhibited 32% silencing activity within 24h of post transfection. Obtained results directed us that the hmPCL-siRNA nanoformulation could be an efficient tool in siRNA mediated therapy for knocking down the infected cells. FROM THE CLINICAL EDITOR: siRNA could be used in cancer therapy if naked nucleic acid could be transported using a suitable carrier. In this article, the authors developed a nano-carrier system using mesoporous polycaprolactone (hmPCL) and showed its efficacy in knocking down cancer cells. This approach may open another way of gene therapy.

Nanoniobia modification of CdS photoanode for an efficient and stable photoelectrochemical cell.

Herein we report the surface modification of a CdS film by niobia nanoparticles via thioglycerol as an organic linker and thus fabricate an efficient and a stable photoanode for a photoelectrochemical (PEC) cell. We have synthesized three differenly sized (∼3, ∼6 ,and ∼9 nm) niobia nanoparticles by a hydrothermal synthesis approach and have further investigated the particle-size-dependent PEC performance of the nanoparticle-modified CdS photoanode. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) confirm the formation of Nb2O5 nanoparticles that are prepared via decomposition of the niobium peroxo complex during the hydrothermal reaction and reveal the presence of surface OH(-) groups over niobia nanoparticles that impart a high catalytic property to a material. The nano-Nb2O5-modified photoanode displayed a 23-fold higher power conversion efficiency compared to that of CdS. This modified structure increases the open circuit voltage (OCV) from 0.65 to 0.77 V, which is attributed to the nano-Nb2O5-induced surface passivation effect over bare CdS. Linking of nanoparticles on the CdS surface improves the photocorrosion stability of the CdS photoanode for even longer than 4 h in contrast to the tens of minutes for the base CdS surface. The uniform coverage of the CdS photoanode surface by niobia nanoparticles is thus found to be the controlling parameter for achieving a higher PEC performance and stability of the photoanode. This finding directed us to design an improved CdS photoanode for efficient and prolonged PEC hydrogen generation from a PEC cell.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 µg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

Nitric oxide releasing novel amino acid-derived polymeric nanotherapeutic with anti-inflammatory properties for rapid wound tissue regeneration.

Endogenous gasotransmitter nitric oxide (NO) is a central signalling molecule that modulates wound healing by maintaining homeostasis, collagen formation, wound contraction, anti-microbial action and accelerating tissue regeneration. The optimum delivery of NO using nanoparticles (NPs) is clinically challenging; hence, it is drawing significant attention in wound healing. Herein, a novel polymeric nanoplatform loaded with sodium nitroprusside (SP) NPs was prepared and used for wound healing to obtain the sustained release of NO in therapeutic quantities. SP NPs-induced excellent proliferation (∼300%) of mouse fibroblast (L929) cells was observed. With an increase in the SP NPs dose at 200 µg mL-1 concentration, a 200% upsurge in proliferation was observed along with enhanced migration, and only 17.09 h were required to fill the 50% gap compared to 37.85 h required by the control group. Further, SP NPs showed an insignificant impact on the coagulation cascade, revealing safe wound-healing treatment when tested in isolated rat RBCs. Additionally, SP NPs exhibited excellent angiogenic activity at a 10 µg mL-1 dose. Moreover, the formulated SP nanoformulation is non-irritant, non-toxic, and does not produce any skin sensitivity reaction on the rat's skin. Further, an in vivo wound healing study revealed that within 11 days of treatment with SP nanoformulation, 99.2 ± 1.0% of the wound was closed, while in the control group, only 45.5 ± 3.8% was repaired. These results indicate that owing to sustained NO release, the SP NP and SP nanoformulations are paramount with enormous clinical potential for the regeneration of wound tissues.

Facile cost-effective green synthesis of carbon dots: selective detection of biologically relevant metal ions and synergetic efficiency for treatment of cancer.

A facile cost-effective green synthesis approach has been used to synthesize carbon-dot (CDs) from the Kernel part of theAzadirachta Indicaseeds and investigated their fluorescent and metal ions sensing capability and also used for the delivery of drugs. Metallic ions such as Ca2+, K+, Na+, Fe3+,and Zn2+which are biologically important for many reactions and are selectively detected through the novel CDs. The resultant dot size of CDs (∼4 nm) is useful to eliminate the 'Achilles heel' problems, which is associated with the Zn2+in the body and its detection is a very challenging task. It is found that the sensitivity of CDs for the detection of Zn2+can be regulated by using different solvents. These CDs can also be used as a sensing probe for the selective detection of Fe3+at a very low concentration of solution (∼5 µM). The synthesis method of CDs reported here is cost-effective, very fast and it is highly selective towards Fe3+and Zn2+. Due to the fast response capability of these CDs, logic gate operation is achieved and it provides a new understanding to construct potential next-generation molecular devices for the detection of different biomolecules with high selectivity. Additionally, these CDs are biocompatible against normal healthy cells, capable of loading small biomolecules and drugs due to their porous nature, and exhibited potential impact for breast cancer therapy. It is observed that a significant synergic therapeutic effect of CDs loaded with doxorubicin against breast cancer cells is very promising. Thus, the CDs reported herein in this work have been synthesized through a green synthesis approach and can be used as a molecular probe for the detection of metal ions as well as for drug delivery applications.

Progress in Treatment and Diagnostics of Infectious Disease with Polymers.

In this era of advanced technology and innovation, infectious diseases still cause significant morbidity and mortality, which need to be addressed. Despite overwhelming success in the development of vaccines, transmittable diseases such as tuberculosis and AIDS remain unprotected, and the treatment is challenging due to frequent mutations of the pathogens. Formulations of new or existing drugs with polymeric materials have been explored as a promising new approach. Variations in shape, size, surface charge, internal morphology, and functionalization position polymer particles as a revolutionary material in healthcare. Here, an overview is provided of major diseases along with statistics on infection and death rates, focusing on polymer-based treatments and modes of action. Key issues are discussed in this review pertaining to current challenges and future perspectives.

Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration.

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

Triangular core-shell ZnO@SiO2 nanoparticles.

Well packed! Core-shell nanostructures composed of ZnO particles encapsulated in an equilateral triangular SiO2 shell are reported for the first time. The quantum-confinement effects within the nanostructures can be used to tune their properties for optoelectronic applications.

Poly(N-acryloylglycine-acrylamide) Hydrogel Mimics the Cellular Microenvironment and Promotes Neurite Growth with Protection from Oxidative Stress.

In this work, the glycine-based acryloyl monomer is polymerized to obtain a neurogenic polymeric hydrogel for regenerative applications. The synthesized poly(N-acryloylglycine-acrylamide) [poly(NAG-b-A)] nanohydrogel exhibits high swelling (∼1500%) and is mechanically very stable, biocompatible, and proliferative in nature. The poly(NAG-b-A) nanohydrogel provides a stable 3D extracellular mimetic environment and promotes healthy neurite growth for primary cortical neurons by facilitating cellular adhesion, proliferation, actin filament stabilization, and neuronal differentiation. Furthermore, the protective role of the poly(NAG-b-A) hydrogel for the neurons in oxidative stress conditions is revealed and it is found that it is a clinically relevant material for neuronal regenerative applications, such as for promoting nerve regeneration via GSK3ß inhibition. This hydrogel additionally plays an important role in modulating the biological microenvironment, either as an agonist and antagonist or as an antioxidant. Furthermore, it favors the physiological responses and eases the neurite growth efficiency. Additionally, we found out that the conversion of glycine-based acryloyl monomers into their corresponding polymer modulates the mechanical performance, mimics the cellular microenvironment, and accelerates the self-healing capability due to the responsive behavior towards reactive oxygen species (ROS). Thus, the p(NAG-b-A) hydrogel could be a potential candidate to induce neuronal regeneration since it provides a physical cue and significantly boosts neurite outgrowth and also maintains the microtubule integrity in neuronal cells.

Azadirachta indica Seed Derived Carbon Nanocapsules: Cell Imaging, Depolarization of Mitochondrial Membrane Potential, and Dose-Dependent Control Death of Breast Cancer.

In this work, a series of mesoporous carbon nanocapsules (mCNS) of size below 10 nm have been prepared from Azadirachta indica seeds with a very easy and cost-effective approach. These nanocapsules can emit red and green light and are effective for cell imaging. Further, these carbon nanocapsules are biocompatible toward the normal healthy cells, however, they possess modest cytotoxicity against the MCF-7 (human breast cancer) and triple-negative breast cancer (TNBC) (MDA- MB-231 breast cancer cells), and the rate of killing cancer cells strongly depends on the dose of mCNCs. Further, the mitochondrial membrane potential and apoptosis assay were performed to analyze the therapeutic significance of these nanocapsules to kill breast cancer. Results showed that these carbon nanocapsules can depolarize the mitochondrial membrane potential alone (without using conventional drugs) and can change the physiological parameters and cellular metabolic energy of the cancer cells and kill them. The apoptosis results confirmed the death of breast cancer cells in the form of apoptosis and necrosis. Moreover, the results suggested that the porous carbon nanocapsules (mCNCs) reported herein can be used as a potential candidate and useful for the theranostic applications such as for cancer cell detection and therapy without using any conventional drugs.

Protein Immobilization on Heterogeneous (SiO2/ZnO) Hollow-Mesoporous Nanocapsules Prepared by Imprinting CPMV: Drug Delivery and Possibility of Immunological Applications.

Herein, we report the protein immobilization and stability studies of heterogeneous hollow mesoporous nanocapsules (Hhmn) for drug and protein delivery. The final results of the diverse precursors such as TEOS, TMOS, APTES, and zinc acetate on the formation of the hollow-mesoporous architecture of nanocapsules have been assimilated in this work. Three types of Hhmn of various sizes were synthesized. Among the three Hhmn, sample I and II nanocapsules were synthesized in the presence of zinc acetate and were identified to be amorphous in nature. Sample III nanocapsules synthesized in the absence of zinc acetate were analogous to the other two synthesized samples. Physiochemical analysis showed the formation of zinc phosphate in the silica matrix for the samples when synthesized with zinc acetate. Specific surface area analysis revealed that sample III has a relatively higher specific surface area. Further, the drug/dye loading and release capacity for the nanocapsules were studied using doxorubicin (DOX) and imatinib mesylate (IM) as model anticancerous drugs and rhodamine 6G as a model dye. Among the synthesized nanocapsules, sample III was shown to have a higher loading capacity for DOX (∼128 µg). From the release kinetic studies of drug/dye, sample III nanocapsules demonstrate a controlled release pattern of DOX and IM. Additionally, protein adsorption and stability studies of samples I and II revealed that the BSA adsorption capacity increases with the increase in the initial concentration of BSA. Furthermore, analysis of the release profiles of BSA and OVA leads to the conclusion that the heterogeneous nanocapsules show a higher loading capacity and sustained release pattern toward OVA. These properties of the nanocapsules highlight their path to immunological applications.

Polymeric Nanoparticle Based Diagnosis and Nanomedicine for Treatment and Development of Vaccines for Cerebral Malaria: A Review on Recent Advancement.

Cerebral malaria occurs due to Plasmodium falciparum infection, which causes 228 million infections and 450,000 deaths worldwide every year. African people are mostly affected with nearly 91% cases, of which 86% are pregnant women and infants. India and Brazil are the other two countries severely suffering from malaria endemicity. Commonly used drugs have severe side effects, and unfortunately no suitable vaccine is available in the market today. In this line, this review is focused on polymeric nanomaterials and nanocapsules that can be used for the development of effective diagnostic strategies, nanomedicines, and vaccines in the management of cerebral malaria. Further, this review will help scientists and medical professionals by updating the status on the development stages of polymeric nanoparticle based diagnostics, nanomedicines, and vaccines and strategies to eradicate cerebral malaria. In addition to this, the predominant focus of this review is antimalarial agents based on polymer nanomedicines that are currently in the preclinical and clinical trial stages, and potential developments are suggested as well. This review further will have an important social and commercial impact worldwide for the development of polymeric nanomedicines and strategies for the treatment of cerebral malaria.

Targeted specific inhibition of bacterial and Candida species by mesoporous Ag/Sn-SnO2 composite nanoparticles: in silico and in vitro investigation.

Invasive bacterial and fungal infections have notably increased the burden on the health care system and especially in immune compromised patients. These invasive bacterial and fungal species mimic and interact with the host extracellular matrix and increase the adhesion and internalization into the host system. Further, increased resistance of traditional antibiotics/antifungal drugs led to the demand for other therapeutics and preventive measures. Presently, metallic nanoparticles have wide applications in health care sectors. The present study has been designed to evaluate the advantage of Ag/Sn-SnO2 composite nanoparticles over the single oxide/metallic nanoparticles. By using in silico molecular docking approaches, herein we have evaluated the effects of Ag/Sn-SnO2 nanoparticles on adhesion and invasion responsible molecular targets such as LpfD (E. coli), Als3 (C. albicans) and on virulence/resistance causing PqsR (P. aeruginosa), RstA (Bmfr) (A. baumannii), FoxA (K. pneumonia), Hsp90 and Cyp51 (C. albicans). These Ag/Sn-SnO2 nanoparticles exhibited higher antimicrobial activities, especially against the C. albicans, which are the highest ever reported results. Further, Ag/Sn-SnO2 NPs exhibited interaction with the heme proionate residues such as Lys143, His468, Tyr132, Arg381, Phe105, Gly465, Gly464, Ile471 and Ile304 by forming hydrogen bonds with the Arg 381 residue of lanosterol 1 4α-demethylase and increased the inhibition of the Candida strains. Additionally, the Ag/Sn-SnO2 nanoparticles exhibited extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species followed by several molecular pathways which indicated that it can be used to eliminate the resistance to traditional antibiotics.

Targeted and Enhanced Antimicrobial Inhibition of Mesoporous ZnO-Ag2O/Ag, ZnO-CuO, and ZnO-SnO2 Composite Nanoparticles.

In this work, mesoporous (pore size below 4 nm) composite nanoparticles of ZnO-Ag2O/Ag, ZnO-CuO, and ZnO-SnO2 of size d ≤ 10 nm (dia.) have been synthesized through the in situ solvochemical reduction method using NaBH4. These composite nanoparticles exhibited excellent killing efficacy against Gram-positive/negative bacterial and fungal strains even at a very low dose of 0.010 µg/mL. Additionally, by applying the in silico docking approach, the nanoparticles and microorganism-specific targeted proteins and their interactions have been identified to explain the best anti-bacterial/anti-fungal activities of these composites. For this purpose, the virulence and resistance causing target proteins such as PqsR, RstA, FosA, and Hsp90 of Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Candida albicans have been identified to find out the best inhibitory action mechanisms involved. From the in vitro study, it is revealed that all the composite nanoparticle types used here can act as potent antimicrobial components. All the composite nanoparticles have exhibited excellent inhibition against the microorganisms compared to their constituent single metal or metal oxide nanoparticles. Among the nanoparticle types, the ZnO-Ag2O/Ag composite nanoparticles exhibited the best inhibition activity compared to the other reported nanoparticles. The microorganisms which are associated with severe infections lead to the multidrug resistance and have become a huge concern in the healthcare sector. Conventional organic antibiotics are less stable at a higher temperature. Therefore, based on the current demands, this work has been focused on designing inorganic antibiotics which possess stability even under harsh conditions. In this direction, our developed composite nanoparticles were explored for potential uses in the healthcare technology, and they may solve many problems in global emergency and epidemics caused by the microorganisms.

Biomimicked and CPMV-Imprinted Hollow Porous Zinc Phosphate Nanocapsules and Their Therapeutic Efficiency.

Hollow zinc phosphate nanocapsules (hZPNCs) are an alloplastic biomaterial that has been synthesized to deliver chemotherapeutic drugs in a sustained manner. A very simple one-pot synthesis approach has been employed to synthesize hZPNCs by using cowpea mosaic virus (CPMV) in the presence of phosphate buffer (PBS) (0.01 M PBS, pH ∼7.2) with zinc acetate precursor. The synthesis mechanism of hZPNCs relies on the basis of biomineralization, where the precursor molecules initiate mineralization with the help of amino acid residues present on the CPMV capsid. The synthesized hollow nanocapsules were of diameter ∼50-60 nm and porous shell with thickness of ∼4 nm. The cavity performed as a reservoir for the anticancer drugs (DOX and IM). The release kinetic studies show the positive aspect of hZPNCs to be labeled as drug delivery cargo for sustained delivery. In vitro cytotoxic studies of hZPNCs and hZPNCs-chemo drugs on HEK293, HEPG2, and K562 cells were performed. The cytotoxic studies show that hZPNCs-DOX and hZPNCs-IM arrest the cell cycle of carcinoma cells (HEPG2 and K562 cells) at relatively low IC50 and that the inhibition efficiency is dosage dependent. Furthermore, through HRTEM, in vitro cellular interactions of carcinoma cells with hZPNCs and chemo drug-loaded hZPNCs were confirmed by the cryo-sectioning of cells before and after the incubation. These studies revealed the likely endocytic pathway for the nanocapsules entering the cell and executing the specific action of delivering the anticancer drugs. Together, these results reveal the hZPNCs as potential sustained drug delivery agents.

Effective in vitro delivery of paclitaxel by nanocargo of mesoporous polycaprolactone against triple negative breast cancer cells by minimalizing drug dose.

Among the breast cancers, triple negative breast cancer (TNBC) has relatively poor outcomes with a lower survival rate and personalised chemotherapy is the only option available for treatment. Currently in the biomedical domain, nanomaterials with porous morphology have revealed their tremendous possibilities to be used as a nanocarrier in treating cancer by offering void space to encapsulate/entrap biological agents. However, the development of nanocarrier-based targeted therapy with high therapeutic efficacy and fewer side effects to normal cells is always a challenge. Here, we have developed nanocargos based on biodegradable mesoporous PCL (polycaprolactone) of approx. diameter of 75 nm by template removal synthesis techniques. Succeeding the comparative analysis of the nanocarriers, the efficiencies of core shell PCL-mZnO (PZ) and mesoporous PCL (HPZ) to deliver paclitaxel (Taxol/T) into breast cancer cells, is investigated. We found that HPZ nanocapsules have less cytotoxicity and drug loading efficiency of about 600 µg mg-1. The Taxol-loaded nanoparticles (T-HPZ) have exhibited more cytotoxicity than Taxol alone treated cancer cells. Furthermore, T-HPZ treated MDA-MB231 cells are accumulated at G2/M phase of the cell cycle and eventually undergo apoptosis. In support of this, anchorage independent growth of MDA-MB231 cells are significantly inhibited by T-HPZ treatment. Together, our findings suggest that T-HPZ-based paclitaxel (Taxol/T) loaded nanoparticles provide a novel therapeutic option in the treatment of TNBC.

Self-assembled pearl-necklace patterned upconverting nanocrystals with highly efficient blue and ultraviolet emission: femtosecond laser based upconversion properties.

This work reports new findings on the formation of a pearl-necklace pattern in self-assembled upconverting nanocrystals (UCN-PNs) which exhibit strong upconversion emission under an NIR excitation source of a femtosecond laser (Fs-laser). Each nano-necklace consists of several upconversion nanoparticles (UCNPs) having a size ca. 10 ± 1 nm. UCN-PNs are arranged in a self-organized manner to form necklace type chains with an average length of 140 nm of a single row of nanoparticles. Furthermore, UCN-PNs are comprised of UCNPs with an average interparticle separation of ca. 4 nm in each of the nanonecklace chains. Interestingly, these UCN-PNs exhibit high energy upconversion especially in the UV region on interaction with a 140 Fs-laser pulse duration at 80 MHz repetition rate and intense blue emission at 450 nm on interaction with a 900 nm excitation source is obtained. The preparation of self-assembled UCNPs is easy and they are very stable for a longer period of time. The emission (fluorescence/luminescence) intensity is very high which can make them unique in innumerable industrial and bio-applications such as for disease diagnosis and therapeutic applications by targeting the infected cells with enhanced efficiency.