Ameliorating the antitumor activity of gemcitabine against breast tumor using αvß3 integrin-targeting lipid nanoparticles.

OBJECTIVE: The main objective is to formulate solid lipid nanoparticles conjugated with cyclic RGDfk peptide encapsulated with gemcitabine hydrochloride drug for targeting breast cancer. SIGNIFICANCE: The hydrophilic nature of gemcitabine hampers passive transport by cell membrane permeation that may lead to drug resistance as it has to enter the cells via nucleoside transporters. The art of encapsulating the drug in a nanovesicle and then anchoring it with a targeting ligand is one of the present areas of research in cancer chemotherapy. METHODS: In this study, solid lipid nanoparticles were prepared by double emulsification and solvent evaporation method. Cyclic RGDfk and gemcitabine hydrochloride were used as targeting ligands and chemotherapeutic drugs, respectively, for targeting breast cancer. The prepared nanoparticles were evaluated for in vitro and in vivo performance to showcase the targeting efficiency and therapeutic benefits of the gemcitabine-loaded ligand conjugated nanoparticles. RESULTS: When compared with gemcitabine (GEM) and GEM loaded nanoparticles (GSLN), the ligand conjugated GEM nanoparticles (cGSLN) showed superior cytotoxicity, apoptosis, and inhibition of 3D multicellular spheroids in human breast cancer cells (MDA MB 231). The in vivo tumor regression studies in orthotopic breast cancer induced Balb/C mice showed that cGSLN displayed superior tumor suppression and also the targeting potential of the cGSLN toward induced breast cancer. CONCLUSION: Prepared nanoformulations showed enhanced anticancer activity in both 2D and 3D cell culture models along with antitumor efficacy in orthotopic breast cancer mouse models.

Controlling core/shell formation of Nanocubic p-Cu2O/n-ZnO toward enhanced photocatalytic performance.

p-Type Cu2O/n-type ZnO core/shell photocatalysts has been demonstrated to be an efficient photocatalyst as a result of their interfacial structure tendency to reduce the recombination rate of photogenerated electron-hole pairs. Monodispersed Cu2O nanocubes were synthesized and functioned as the core, on which ZnO nanoparticles were coated as the shells having varying morphologies. The evenly distributed ZnO decoration as well as assembled nanospheres of ZnO were carried out by changing the molar concentration ratio of Zn/Cu. The results indicate that the photocatalytic performance is initially increased, owing to formation of small ZnO nanoparticles and production of efficient p-n junction heterostructures. However, with increasing Zn concentration, the decorated ZnO nanoparticles tend to form large spherical assemblies resulting in decreased photocatalytic activity due to the interparticle recombination between the agglomerated ZnO nanoparticles. Therefore, photocatalytic activity of Cu2O/ZnO heterostructures can be optimized by controlling the assembly and morphology of the ZnO shell.

Low-temperature fabrication of alkali metal-organic charge transfer complexes on cotton textile for optoelectronics and gas sensing.

A generalized low-temperature approach for fabricating high aspect ratio nanorod arrays of alkali metal-TCNQ (7,7,8,8-tetracyanoquinodimethane) charge transfer complexes at 140 °C is demonstrated. This facile approach overcomes the current limitation associated with fabrication of alkali metal-TCNQ complexes that are based on physical vapor deposition processes and typically require an excess of 800 °C. The compatibility of soft substrates with the proposed low-temperature route allows direct fabrication of NaTCNQ and LiTCNQ nanoarrays on individual cotton threads interwoven within the 3D matrix of textiles. The applicability of these textile-supported TCNQ-based organic charge transfer complexes toward optoelectronics and gas sensing applications is established.

Role of the templating approach in influencing the suitability of polymeric nanocapsules for drug delivery: LbL vs SC/MS.

Polymer nanocapsules play an increasingly important role for drug delivery applications. Layer-by-layer (LbL) templated synthesis has received the widest attention to fabricate polymer nanocapsules. However, for drug delivery applications, the LbL approach may not necessarily offer the optimum nanocapsules. We make the first attempt to compare the LbL approach with a more recently developed solid core/mesoporous shell (SC/MS) templated approach in context of their suitability for construction of sub-500 nm sized capsules for drug delivery applications. The nanocapsules of chitosan, poly(allylamine hydrochloride) (PAH), and poly(sodium 4-styrenesulfonate) (PSS) are fabricated using LbL and SC/MS templating approaches and loaded with curcumin, a model lipophilic anticancer drug. The influence of the templating approach on capsule aggregation, polymer loading, drug loading, cellular uptake, and therapeutic efficacy against MCF-7 breast cancer cells is compared in an effort to identify the most suitable fabrication method and polymer material for drug delivery applications. In combination, among different tested nanocapsules, chitosan nanocapsules fabricated using the SC/MS approach are found to be the most promising candidate that demonstrates the optimum cytotoxic efficiency and significant potential for drug delivery.

Serotonin-Functionalized Vit-E Nanomicelles for Targeting of Irinotecan to Prostate Cancer Cells.

Receptor-mediated endocytosis is key in the success of targeted nanomedicines for the treatment of cancer. Various receptors have been explored for the active targeting of anticancer drugs to avoid the drawbacks of conventional anticancer drugs. This research work aimed to investigate the potential of serotonin (ST)-conjugated Vit-E nanomicelles for the targeted delivery of irinotecan hydrochloride (IRI) to human prostate cancer cells. A ST receptor-targeting conjugate was synthesized by conjugating ST and d-α-tocopheryl polyethylene glycol succinate via a two-step synthesis reaction. The developed formulation demonstrated a size of about 14 nm, a negative zeta potential of around -20 mV, a high drug encapsulation efficiency, and sustained drug release over 48 h. Cytotoxicity studies revealed that ST-conjugated, IRI-loaded nanomicelles (IRI-STNM) were not only toxic to human prostate cancer cells but also eradicate these cells present in the form of 3D spheroids. This cytotoxicity of IRI-STNM was mediated through induction of apoptosis, reactive oxygen species generation, change in mitochondrial membrane potential, and inhibition of cell migration. Further, IRI-STNM performed significantly better than the native IRI and nontargeted nanomicelles, which was led by a higher cellular uptake of IRI-STNM, indicating the role of ST in targeting of drug-loaded nanomicelles.

Current trends and challenges in cancer management and therapy using designer nanomaterials.

Nanotechnology has the potential to circumvent several drawbacks of conventional therapeutic formulations. In fact, significant strides have been made towards the application of engineered nanomaterials for the treatment of cancer with high specificity, sensitivity and efficacy. Tailor-made nanomaterials functionalized with specific ligands can target cancer cells in a predictable manner and deliver encapsulated payloads effectively. Moreover, nanomaterials can also be designed for increased drug loading, improved half-life in the body, controlled release, and selective distribution by modifying their composition, size, morphology, and surface chemistry. To date, polymeric nanomaterials, metallic nanoparticles, carbon-based materials, liposomes, and dendrimers have been developed as smart drug delivery systems for cancer treatment, demonstrating enhanced pharmacokinetic and pharmacodynamic profiles over conventional formulations due to their nanoscale size and unique physicochemical characteristics. The data present in the literature suggest that nanotechnology will provide next-generation platforms for cancer management and anticancer therapy. Therefore, in this critical review, we summarize a range of nanomaterials which are currently being employed for anticancer therapies and discuss the fundamental role of their physicochemical properties in cancer management. We further elaborate on the topical progress made to date toward nanomaterial engineering for cancer therapy, including current strategies for drug targeting and release for efficient cancer administration. We also discuss issues of nanotoxicity, which is an often-neglected feature of nanotechnology. Finally, we attempt to summarize the current challenges in nanotherapeutics and provide an outlook on the future of this important field.

SERS and fluorescence-based ultrasensitive detection of mercury in water.

The development of reliable and ultrasensitive detection marker for mercury ions (Hg2+) in drinking water is of great interest for toxicology assessment, environmental protection and human health. Although many Hg2+ detection methods have been developed, only few offer sensitivities below 1pM. Herein, we describe a simple histidine (H) conjugated perylene diimide (PDI) bolaamphiphile (HPH) as a dual-responsive optical marker to develop highly selective and sensitive probe as visible (sol-to-gel transformation), fluorescence and SERS-based Hg2+sensor platform in the water. Remarkably, HPH as a SERS marker supported on Au deposited monodispersed nanospheres monolayers (Au-MNM) of polystyrene offers an unprecedented selectivity and the best ever reported detection limit (LOD) of 60 attomolar (aM, 0.01 parts-per-quadrillion (ppq)) for Hg2+ in water. This is ten orders of magnitude lower than the United States Environmental Protection Agency (USEPA) tolerance limit of Hg2+ in drinking water (10nM, 2 ppb). This simple and effective design principle of host-guest interactions driven fluorescence and SERS-based detection may inspire the future molecular engineering strategies for the development of ultrasensitive toxic analyte sensor platforms.

Effect of preoperative incentive spirometry on fentanyl-induced cough: a prospective, randomized, controlled study.

BACKGROUND: Fentanyl-induced cough (FIC) has a reported incidence of 13-65% on induction of anesthesia. Incentive spirometry (IS) creates forceful inspiration, while stretching pulmonary receptors. We postulated that spirometry just before the fentanyl (F) bolus would decrease the incidence and severity of FIC. METHODS: This study enrolled 200 patients aged 18-60 years and with American Society of Anesthesiologists status I or II. The patients were allocated to two groups of 100 patients each depending on whether they received preoperative incentive spirometry before fentanyl administration. Patients in the F+IS group performed incentive spirometry 10 times just before an intravenous bolus of 3 µg/kg fentanyl in the operating room. The onset time and number of coughs after fentanyl injection were recorded as primary outcomes. Any significant changes in blood pressure, heart rate, or adverse effects of the drug were recorded as secondary outcomes. RESULTS: Patients in the F+IS group had a significantly lower incidence of FIC than in the F group (6% vs. 26%) (P < 0.05). The severity of cough in the F+IS group was also significantly lower than that in group F (mild, 5 vs. 17; moderate 1 vs. 7; severe, 0 vs. 2) (P < 0.05). The median onset time was comparable in both groups (9 s [range: 6-12 s] in both groups). CONCLUSIONS: Preoperative incentive spirometry significantly reduces the incidence and severity of FIC when performed just before fentanyl administration.

Perioperative neonatal and paediatric blood transfusion.

Paediatric patients undergoing surgical procedures commonly require some volume of blood or blood component replacement in the perioperative period. Paediatric patients undergoing major surgery associated with substantial blood loss should be evaluated pre-operatively. Pre-operative correction of anaemia may be done considering the age, plasma volume status, clinical status and comorbidities. Maximum allowable blood loss (MABL) for surgery must be calculated, and appropriate quantity of blood and blood components should be arranged. Intraoperative monitoring of blood loss should be done, and volume of transfusion should be calculated in a protocol based manner considering the volemia and the trigger threshold for transfusion for the patient and the MABL. Early haemostasis should be achieved by judicious administration of red blood cells, blood components and pharmacological agents.

Zinc oxide/silver nanoarrays as reusable SERS substrates with controllable 'hot-spots' for highly reproducible molecular sensing.

HYPOTHESIS: The reproducible surface enhanced Raman scattering (SERS)-based sensing of an analyte relies on high quality SERS substrates that offer uniformity over large areas. Uniform ZnO nanoarrays are expected to offer an appropriate platform for SERS sensing. Moreover, since ZnO has good photocatalytic properties, controllable decoration of silver nanoparticles on ZnO nanoarrays may offer an additional opportunity to clean up SERS substrates after each sensing event. EXPERIMENTS: This study employs a facile soft chemical synthesis strategy to fabricate Raman-active and recyclable ZnO/Ag nanorod arrays as reproducible SERS substrates. Arrays of ZnO nanorods were synthesized using hydrothermal method, which was followed by controllable decoration of ZnO with silver nanoparticles (AgNPs) using an electroless plating technique. FINDINGS: The uniform density of SERS-active 'hot-spots' on ZnO nanoarrays could be controlled on a large 1×1 cm(2) substrate. These ZnO/Ag nanoarrays showed high reproducibility (0.132 RSD) towards acquiring SERS spectra of rhodamine B (RB) at 30 random locations on a single substrate. The photocatalytic nature of ZnO/Ag semiconductor/metal hybrid endowed these substrates with reusability characteristics. By controlling metal loading on a semiconductor surface, photocatalytic activity and high SERS performance can be integrated within a single package to obtain high quality, reproducible, stable and recyclable SERS substrates.

Spiral patterns of gold nanoclusters in silicon (100) produced by metal vapour vacuum arc implantation of gold ions.

Self-assembled gold nanoclusters are attractive building blocks for future nanoscale sensors and optical devices due to their exciting catalytic properties. In this work, we report direct bottom-up synthesis of spiral patterns of gold nanoclusters in silicon (100) substrates by Au ion implantation followed by thermal annealing. This unique phenomenon is observed only above a critical threshold implantation dose and annealing temperature. Systematic study by electron microscopy, analytical x-ray diffraction and atomic force microscopy shows the temperature- and time-dependent nucleation, growth of Au nanoclusters and evolution of the spiral patterns. The observed patterns of gold nanoclusters bear a resemblance to the spiral growth prevalent in some directionally solidified eutectic alloys. Based on this systematic study of the growth and morphology of nanoclusters, a tentative model has been proposed for the formation mechanism of this unusual self-assembled pattern in an amorphous Si/Au system. This model shows that melting of the implanted layer is essential and without which no spiral patterns are observed. A better understanding of this self-assembly process will open up new ways to fabricate ordered arrays of gold nanoclusters in silicon substrates for seeding selective growth of one-dimensional nanostructures.