ヴィーラナラヤナン スリワニ

In response to the escalating antibiotic resistance in multidrug-resistant pathogens, we propose an innovative phagemid-based capsid system to generate CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) for targeted therapy against multidrug-resistant Staphylococcus aureus. Our optimized phagemid system maximizes AB-capsid yield and purity, showing a positive correlation with phagemid copy number. Notably, an 8.65-fold increase in copy number results in a 2.54-fold rise in AB-capsid generation. Phagemids carrying terL-terS-rinA-rinB (prophage-encoded packaging site genes) consistently exhibit high packaging efficiency, and the generation of AB-capsids using lysogenized hosts with terL-terS deletion resulted in comparatively lower level of wild-type phage contamination, with minimal compromise on AB-capsid yield. These generated AB-capsids selectively eliminate S. aureus strains carrying the target gene while sparing non-target strains. In conclusion, our phagemid-based capsid system stands as a promising avenue for developing sequence-specific bactericidal agents, offering a streamlined approach to combat antibiotic-resistant pathogens within the constraints of efficient production and targeted efficacy.

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.

In response to the escalating global threat of antimicrobial resistance, our laboratory has established a phagemid packaging system for the generation of CRISPR-Cas13a-antimicrobial capsids targeting methicillin-resistant Staphylococcus aureus (MRSA). However, a significant challenge arose during the packaging process: the unintentional production of wild-type phages alongside the antimicrobial capsids. To address this issue, the phagemid packaging system was optimized by strategically incorporated silent mutations. This approach effectively minimized contamination risks without compromising packaging efficiency. The study identified the indispensable role of phage packaging genes, particularly terL-terS, in efficient phagemid packaging. Additionally, the elimination of homologous sequences between the phagemid and wild-type phage genome was crucial in preventing wild-type phage contamination. The optimized phagemid-LSAB(mosaic) demonstrated sequence-specific killing, efficiently eliminating MRSA strains carrying target antibiotic-resistant genes. While acknowledging the need for further exploration across bacterial species and in vivo validation, this refined phagemid packaging system offers a valuable advancement in the development of CRISPR-Cas13a-based antimicrobials, shedding light on potential solutions in the ongoing battle against bacterial infections.

Bacteriophages, the viruses that infect and replicate within bacteria, have long been recognized as potential therapeutic agents against bacterial infections [...]

Non-menstrual toxic shock syndrome (non-mTSS) is a life-threatening disease caused by <italic>Staphylococcus aureus</italic> strains producing superantigens, such as staphylococcal enterotoxins A, B, C, and toxic shock syndrome toxin-1 (TSST-1). However, little is known about why the TSS cases are rare, although <italic>S. aureus</italic> strains frequently carry a <italic>tst</italic> gene, which encodes TSST-1. To answer this question, the amount of TSST-1 produced by 541 clinical isolates was measured in both the presence and absence of serum supplementation to growth media. Then a set of <italic>S. aureus</italic> strains with similar genetic backgrounds isolated from patients presenting with non-mTSS and those with clinical manifestations other than non-mTSS was compared for their TSST-1 inducibility by human serum, and their whole-genome sequences were determined. Subsequently, the association of mutations identified in the <italic>tst</italic> promoter of non-mTSS strains with TSST-1 inducibility by human serum was evaluated by constructing promoter replacement mutants and green fluorescent protein (GFP) reporter recombinants. Results showed that 39 out of 541 clinical isolates (7.2%), including strains isolated from non-mTSS patients, had enhanced production of TSST-1 in the presence of serum. TSST-1 inducibility by human serum was more clearly seen in non-mTSS strains of clonal complex (CC)-5. Moreover, the whole-genome sequence analysis identified a set of sequence variations at a putative SarA-binding site of the <italic>tst</italic> promoter. This sequence variation was proven to be partially responsible for the induction of TSST-1 production by human serum. We conclude that the onset of staphylococcal toxic shock syndrome caused by TSST-1-producing CC-5 strains seem at least partially initiated by serum induction of TSST-1, which is regulated by the mutation of putative SarA-binding site at the <italic>tst</italic> promoter.

Cancer, especially the solid tumor sub-set, poses considerable challenges to modern medicine owing to the unique physiological characteristics and substantial variations in each tumor’s microenvironmental niche fingerprints. Though there are many treatment methods available to treat solid tumors, still a considerable loss of life happens, due to the limitation of treatment options and the outcomes of ineffective treatments. Cancer cells evolve with chemo- or radiation-treatment strategies and later show adaptive behavior, leading to failed treatment. These challenges demand tailored and individually apt personalized treatment methods. Bacteriophages (or phages) and phage-based theragnostic vectors are gaining attention in the field of modern cancer medicine, beyond their bactericidal ability. With the invention of the latest techniques to fine-tune phages, such as in the field of genetic engineering, synthetic assembly methods, phage display, and chemical modifications, noteworthy progress in phage vector research for safe cancer application has been realized, including use in pre-clinical studies. Herein, we discuss the distinct fingerprints of solid tumor physiology and the potential for bacteriophage vectors to exploit specific tumor features for improvised tumor theragnostic applications.

Cardiac tissue engineering (CTE) aims to generate potential scaffolds to mimic extracellular matrix (ECM) for recreating the injured myocardium. Highly porous scaffolds with properties that aid cell adhesion, migration and proliferation are critical in CTE. In this study, electrospun porous poly (l-lactic acid) (PLLA) porous scaffolds were fabricated and modified with different ECM derived proteins such as collagen, gelatin, fibronectin and poly-L-lysine. Subsequently, adult human cardiac fibroblasts (AHCF) were cultured on the protein modified and unmodified fibers to study the cell behavior and guidance. Further, the cytotoxicity and reactive oxygen species (ROS) assessments of the respective fibers were performed to determine their biocompatibility. Excellent cell adhesion and proliferation of the cardiac fibroblasts was observed on the PLLA porous fibers regardless of the surface modifications. The metabolic rate of cells was on par with the conventional cell culture ware while the proliferation rate surpassed the latter by nearly two-folds. Proteome profiling revealed that apart from being an anchorage platform for cells, the surface topography has modulated significant expression of the cellular proteome with many crucial proteins responsible for cardiac fibroblast growth and proliferation.

Cancer is a highly intelligent system of cells, that works together with the body to thrive and subsequently overwhelm the host in order for its survival. Therefore, treatment regimens should be equally competent to outsmart these cells. Unfortunately, it is not the case with current therapeutic practices, the reason why it is still one of the most deadly adversaries and an imposing challenge to healthcare practitioners and researchers alike. With rapid nanotechnological interventions in the medical arena, the amalgamation of diagnostic and therapeutic functionalities into a single platform, theranostics provides a never before experienced hope of enhancing diagnostic accuracy and therapeutic efficiency. Additionally, the ability of these nanotheranostic agents to perform their actions on-demand, i.e. can be controlled by external stimulus such as light, magnetic field, sound waves and radiation has cemented their position as next generation anti-cancer candidates. Numerous reports exist of such stimuli-responsive theranostic nanomaterials against cancer, but few have broken through to clinical trials, let alone clinical practice. This review sheds light on the pros and cons of a few such theranostic nanomaterials, especially inorganic nanomaterials which do not require any additional chemical moieties to initiate the stimulus. The review will primarily focus on preclinical and clinical trial approved theranostic agents alone, describing their success or failure in the respective stages.

Materials with efficient potential in imaging as well as therapy are gaining particular attention in current medical research. Photodynamic therapy (PDT) has been recently recognized as a promising treatment option for solid tumors. Still, most of the nanomaterial-based PDT modules either employ an additional photosensitizer or require high power laser sources. Also, they suffer from a lack of responsiveness in the near-infrared (NIR) region. Nanomaterials that could realize PDT independently (without any photosensitizer), at safe laser dose and in the deep tissue penetrative NIR region would definitely be better solid tumor treatment options. Methods: Herein, Cu- and Bi-based bimetal chalcogenide (Cu3BiS3), with absorption in the NIR region was developed. High-performance PDT of cancer and high-contrast x-ray imaging of tumor were performed in vivo. Biocompatibility of the NCs was also assessed in vivo. Results: The highlight of the results was the realization of ultra-low dose NIR laser-mediated PDT, which has not been achieved before, leading to complete tumor regression. This could be a breakthrough in providing a pain- and scar-less treatment option, especially for solid tumors and malignant/benign subcutaneous masses. Though the NCs are active in the photo-thermal therapy (PTT) regime as well, focus is given to the exciting aspect of extremely low power-induced PDT observed here. Conclusion: Their extended in vivo biodistribution with commendable hemo- and histo-compatibilities, along with imaging and multi-therapeutic capabilities, project these Cu3BiS3 NCs as promising, prospective theranostic candidates.

Design of safe and efficient vehicles for the combinatorial delivery of drugs and genetic agents is an emerging requisite for achieving enhanced therapeutic effect in cancer. Even though several nanoplatforms have been explored for the co-delivery of drugs and genetic materials the translation of these systems to clinical phase is still a challenge, mainly due to tedious synthesis procedures, lack of serum stability, inefficient scalability etc. Here in, we report development of reduction and pH sensitive polymeric graft of low molecular weight poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co-delivering drug and siRNA. The polymer was modified with suitable components, which could help in overcoming various systemic and cellular barriers for successful co-delivery of drugs and nucleic acids to cancer cells, using simple chemical reactions. The polymeric derivative could easily self assemble in water to form smooth, spherical micellar structures, indicating their scalability. Doxorubicin and PLK-1 siRNA were selected as model drug and nucleic acid, respectively. Doxorubicin could be loaded in the self assembling micelles with an optimum loading content of ∼8.6% w/w and efficient siRNA complexation was achieved with polymer/siRNA weight ratios >40. The polyplexes were stabilized in physiological saline by coating with bovine serum albumin (BSA). Stable drug loaded nanoplexes, for clinical administration, could be easily formulated by gently dispersing them in physiological saline containing appropriate amount of albumin. Drug release from the nanoplexes was significantly enhanced at low pH (5) and in the presence of 10 mM glutathione (GSH) showing their dual stimuli sensitive nature. In vitro cell proliferation assay and in vivo tumor regression study have shown synergistic effect of the drug loaded nanoplexes in inhibiting cancer cell proliferation. Facile synthesis steps, scalability and ease of formulation depict excellent clinical translation potential of the proposed nanosystem.

The anti-apoptotic defense mechanism of cancer cells poses a major hurdle which makes chemotherapy less effective. Combinatorial delivery of drugs and siRNAs targeting anti-apoptotic proteins is a vital means for improving therapeutic effects. The present study aims at designing a suitable carrier which can effectively co-deliver doxorubicin and plk1 siRNA to tumor cells. Low molecular weight poly(styrene-alt-maleic anhydride) was chemically modified via a click reaction to obtain a cationic amphiphilic polymer for the co-delivery of therapeutic agents. Short glycol chains were utilized as linker molecules for grafting which in turn imparted a stealth nature and minimized plasma protein adsorption to the polymeric surface. Isonicotinic acid was grafted to the polymer due to its ability to penetrate the endolysosomal membrane and arginine-lysine conjugates were embedded for complexing siRNA. The polymer was able to self-assemble in to smooth, spherical micellar structures with a CMC of ∼3 μg mL-1. The particle size of the micelles was ∼14-30 nm as depicted using TEM and FESEM. Atomic force microscopic analysis showed an average height of ∼12 nm for the polymeric micelles. An optimum doxorubicin loading of ∼9% w/w was achieved with the micelles using a dialysis method. Effective complexation of siRNA occurred above a polymer/siRNA weight ratio of 10 without any significant change in the particle size. Doxorubicin and fluorescent labeled siRNA loaded micelles exhibited excellent co-localization within the cytoplasm of MCF-7 cells. The synergistic effect of the active agents in inhibiting tumor cell proliferation was depicted using an MTT assay and visualized using calcein/propidium iodide staining of the treated cells. Co-administration of doxorubicin and plk1 siRNA in EAT tumor bearing Swiss albino mice using the cationic micelles significantly enhanced the antitumor efficacy.

Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2-XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies.

A simple, crude Jatropha curcas (JC) oil-based synthesis approach, devoid of any toxic phosphine and pyrophoric ligands, to produce size and shape tuned CdSe QDs and a further copper sulfide (Cu2S) encasing is presented. The QDs exhibited excellent photoluminescent properties with narrow band gap emission. Furthermore, the Cu2S shell rendered additional cytocompatibility and stability to the hybrid nanomaterial, which are major factors for translational and clinical applications of QDs. The nanocomposites were PEGylated and folate conjugated to augment their cytoamiability and enhance their specificity towards cancer cells. The nanohybrids possess potentials for visible, near infrared (NIR), photoacoustic (PA) and computed tomography (μCT) imaging. The diverse functionality of the composite was derived from the multi-channel imaging abilities and thermal competence on NIR laser irradiation to specifically actuate the photo-thermal ablation of brain cancer cells.

The in vitro and in vivo uptake, toxicological analysis and anti-angiogenic theranostic prospect of FITC loaded (FITC-Si) and suramin loaded (Sur-Si) silica nanoparticles are presented. FITC/suramin encapsulated silica nanoparticles (NPs) with an average size of <30 nm were synthesized. The uptake of FITC-Si by human umbilical vein endothelial cells (HuVECs) (in vitro) and by early stage medaka embryos (in vivo) was monitored by fluorescence microscopy. The nanoformulation was found to be biocompatible with both cells and embryos. The cytotoxicity analysis, tubulogenesis and migration assay confirmed the anti-angiogenic potential of Sur-Si NPs in HuVECs. The imaging of medaka embryos exposed to FITC-Si, their survival and hatching rate and biocompatibility post FITC-Si exposure were documented. The in vivo drug delivery mediated anti-angiogenic potential of Sur-Si NPs was assessed by survival and hatching rate analysis along with morphological indicators. At higher concentrations, Sur-Si proved lethal to embryos, whereas at lower concentrations it was rather an efficient anti-angiogenic formulation leading to malformed vasculogenesis and inhibited intersegmental vessel formation in an efficient dose dependent mode. The results indicate the potential application of such nanoformulation in future anti-angiogenic theranostics.

Multifunctional nanomaterial-based probes have had key impacts on high-resolution and high-sensitivity bioimaging and therapeutics. Typically, NIR-absorbing metal sulfide-based nanocrystals (NCs) are highly assuring due to their unique optical properties. Yet, their in vivo behavior remains undetermined, which in turn undermines their potential bioapplications. Herein, we have examined the application of PEGylated Cu2S NCs as tumor contrast optical nanoprobes as well as investigated the short- and long-term in vivo compatibility focusing on anti-oxidant defense mechanism, genetic material, immune system, and vital organs. The studies revealed an overall safe profile of the NCs with no apparent toxicity even at longer exposure periods. The acquired observations culminate into a set of primary safety data of this nanomaterial and the use of PEGylated Cu2S NCs as promising optical nanoprobes with immense futuristic bioapplications.

A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.

A nanoformulation composed of a ribosome inactivating protein-curcin and a hybrid solid lipid nanovector has been devised against glioblastoma. The structurally distinct nanoparticles were highly compatible to human endothelial and neuronal cells. A sturdy drug release from the particles, recorded upto 72 h, was reflected in the time-dependent toxicity. Folate-targeted nanoparticles were specifically internalized by glioma, imparting superior toxicity and curbed an aggressively proliferating in vitro 3D cancer mass in addition to suppressing the anti-apoptotic survivin and cell matrix protein vinculin. Combined with the imaging potential of the encapsulated dye, the nanovector emanates as a multifunctional anti-cancer system.

Curcin, a type 1 ribosome inactivating protein (RIP) is investigated here for its cellular competence on six mammalian cell lines. Cells exposed to curcin (100 mu g/ml) for 72 h exhibited significant cellular metabolic arrest, with the cancer cell lines being more sensitive. The viability assessment of the cancer cells in a 3D cell culture based assay revealed highly restricted sprouting and proliferation with near to complete dead cell population. Prominent mitochondrial dysfunction, elevated reactive oxygen species levels, nuclear degeneration, structural/mechanical destabilization and suppression of defense mechanisms were imminent with the RIP treated cells. Expression levels of nuclear factor kappa B (NF-kappa B), cytoskeletal focal adhesion kinases (FAK) and vinculin were significantly diminished. Vital cellular organelles as nucleus, mitochondria and actin were severely incapacitated on RIP exposure resulting in multimodal apoptosis and necrosis. The ability of curcin to impart comprehensive shutdown of the cells, especially cancer cells, complemented with its hemocompatibility, opens up possibilities of utilizing this ribotoxin as a prospective therapeutic candidate against cancers of diverse origins.

BACKGROUND: Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy. METHODS: Gold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies. RESULTS: Highly cyto-compatible, 10-15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision. CONCLUSION: The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass. GENERAL SIGNIFICANCE: With multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.

Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions. (C) 2013 Elsevier B.V. All rights reserved.

Cancer is one of the leading causes of death in most parts of the world and is a very serious cause of concern particularly in developing countries. In this work, we prepared and evaluated the aptamer-labeled paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Apt-PTX-PLGA NPs) which can ameliorate drug bioavailability and enable accurate drug targeting to cancer cells with controlled drug release for cancer therapy. Paclitaxel-loaded PLGA nanoparticles (PTX-PLGA NPs) were formulated by a single-emulsion/solvent evaporation method and were further surface-functionalized with a chemical cross-linker bis(sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. The prepared nanoparticles were characterized by atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Cytotoxicity studies were carried out using normal human mammary epithelial cells (HMEC cells) and human glial cancer cells (GI-1 cells) by methylthiazolyldiphenyl-tetrazolium bromide assay and Alamar blue assay, which confirmed that PTX-PLGA NPs with aptamer conjugation (Apt-PTX-PLGA NPs) were comparatively non-toxic to HMEC cells while toxic to GI-1 cancer cells. Cellular uptake of PTX-PLGA NPs with and without aptamer conjugation was studied using GI-1 cells and monitored by confocal microscopy and phase contrast microscopy. Our studies demonstrated significant internalization and retention of nanoparticles inside the cells, inducing apoptosis. The preferential accumulation of PTX-PLGA NPs within the cancer cells were also confirmed by flow cytometry-based uptake studies. The results indicated that Apt-PTX-PLGA NPs could be a promising targeted therapeutic delivery vehicle for cancer treatment. © 2012 Springer-Verlag.

The targeting and therapeutic efficacy of dye- and dual-drug-loaded silica nanoparticles, functionalized with triple targeting ligands specific towards cancer and neoangiogenesis simultaneously, are discussed. This synergized, high-precision, multitarget concept culminates in an elevated uptake of nanoparticles by cancer and angiogenic cells with amplified proficiency, thereby imparting superior therapeutic efficacy against breast cancer cells and completely disabling the migration and angiogenic sprouting ability of activated endothelial cells. The exceptional multimodal efficiency achieved by this single therapeutic nanoformulation holds promise for the synergistic targeting and treatment of the yet elusive cancer and its related angiogenesis in a single, lethal shot.

Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery.

We have synthesized and characterized novel semiconductor nanocrystals of CuAlS2 using simple colloidal route. These nanocrystals exhibited excellent luminescence on par with heavy metal based nanocrystals at green region of visible spectrum. We have successfully accomplished biofunctionalization by using polyethylene glycol moieties thereby rendering biocompatibility to these novel nanocrystals. In addition, by nano-engineering their surface with polyethylene glycol-folate, we could drive these nanocrystals towards over expressed folate receptor cancer cells with high specificity. The utility of these bio-functionalized nanocrystals in cancer imaging was elucidated by confocal studies. We anticipate that these surface modified nanocrystals could be used in diagnostic imaging arena of cancer due to their biocompatibility and stable luminescent property in near future.

We discuss about the utilization of functionalized electrophoretic deposition technique for photovoltaic application encompassing the prospective potential of both functionalization and electrophoretic deposition. We report the fabrication of TiO2 sensitized electrode by electrophoretic deposition of CdSe quantum dots. This method holds the advantage of achieving effective coating of CdSe onto TiO2 electrode by reducing the deposition time to 15 min. Cross-sectional and depth profile elemental analysis revealed the even distribution of CdSe across the TiO2 layer. Ninety percentage of light harvesting efficiency was achieved for the CdSe sensitized electrode affirming the efficacy of sensitization by functionalized electrophoretic deposition. (C) 2012 Elsevier B. V. All rights reserved.

Cancer stands as a leading cause of mortality worldwide and diagnostics of cancer still faces drawbacks. Optical imaging of cancer would allow early diagnosis, evaluation of disease progression and therapy efficiency. To that aim, we have developed highly biocompatible PEG functionalized cadmium chalcogenide based three differently luminescent quantum dots (QDs) (CdS, CdSe and CdTe). Folate targeting scheme was utilized for targeting cancer cell line, MCF-7. We demonstrate the biocompatibility, specificity and efficiency of our nanotool in detection of cancer cells sparing normal cell lines with retained fluorescence of functionalized QDs as parental counterpart. This is the first time report of utilizing three differently fluorescent QDs and we have detailed about the internalization of these materials and time dependent saturation of targeting schemes. We present here the success of utilizing our biocompatible imaging tool for early diagnosis of cancer.

Nanocrystals (NCs) with anisotropic dimensions display polarized emission compared to nano dots. Triangular prisms are good candidates for polarized optical properties and monodisperse triangular NCs are ideal for developing building blocks for novel three-dimensional superlattices due to its anisotropic dimension. Among triangular nanocrystals, CdS nanocrystals are less discussed for the past one decade of research due to the difficulty in its processing method. Though well studied very few methods for developing CdS triangular nanocrystals have been reported, and most are having drawbacks either due to the time consuming process or the products are combination of triangular as well as many other shaped NC or with trap emissions due to defects which are comparable to band emissions limits its applications in full scale. Here, we are presenting a novel method to develop 7 nm CdS triangular NCs that can solve the above mentioned problems, which would augment the usage of CdS triangular crystals for many applications, based on its anisotropic properties.

Target-specific drug delivery system that can transport an effective dosage of anti-cancer drugs to the targeted tumor cells can significantly reduce drug toxicity to the normal cells and increase the therapeutic effect of the drug. In our work, we have evaluated the cytotoxic potential of paclitaxel-loaded silica nanoparticles (Si-PTX NPs) prepared by template-directed stöber synthesis technique. The particles were characterized using transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. We have modified the surface of the drug-loaded particles chemically and conjugated a tumor-specific aptamer (Apt-Si-PTX NPs) to facilitate targeted drug delivery to the cancer cells. In vitro studies carried out demonstrated that the aptamer-conjugated paclitaxel-loaded silica nanoparticles could target the cancer cells with high specificity and destroy them effectively, while sparing the normal cells. This work concludes that the aptamer-tagged paclitaxel-loaded silica nanoparticles are excellent targeting moieties for targeted drug delivery to tumor cells. © 2011 Springer Science+Business Media, LLC.

The use of fluorescent nanomaterials has gained great importance in the field of medical imaging. Many traditional imaging technologies have been reported utilizing dyes in the past. These methods face drawbacks due to non-specific accumulation and photobleaching of dyes. We studied the uptake and internalization of two different sized (30 nm and 100 nm) FITC labeled silica nanoparticles in Human umbilical vein endothelial cell line. These nanomaterials show high biocompatability and are highly photostable inside live cells for increased period of time in comparison to the dye alone. To our knowledge, we report for the first time the use of 30 nm fluorescent silica nanoparticles as efficient endothelial tags along with the well studied 100 nm particles. We also have emphasized the good photostability of these materials in live cells.

This paper presents the synthesis of aqueous cadmium sulfide (CdS) quantum dots (QDs) and silica-encapsulated CdS QDs by reverse microemulsion method and utilized as targeted bio-optical probes. We report the role of CdS as an efficient cell tag with fluorescence on par with previously documented cadmium telluride and cadmium selenide QDs, which have been considered to impart high levels of toxicity. In this study, the toxicity of bare QDs was efficiently quenched by encapsulating them in a biocompatible coat of silica. The toxicity profile and uptake of bare CdS QDs and silica-coated QDs, along with the CD31-labeled, silica-coated CdS QDs on human umbilical vein endothelial cells and glioma cells, were investigated. The effect of size, along with the time-dependent cellular uptake of the nanomaterials, has also been emphasized. Enhanced, high-specificity imaging toward endothelial cell lines in comparison with glioma cells was achieved with CD31 antibody-conjugated nanoparticles. The silica-coated nanomaterials exhibited excellent biocompatibility and greater photostability inside live cells, in addition to possessing an extended shelf life. In vivo biocompatibility and localization study of silica-coated CdS QDs in medaka fish embryos, following direct nanoparticle exposure for 24 hours, authenticated the nanomaterials' high potential for in vivo imaging, augmented with superior biocompatibility. As expected, CdS QD-treated embryos showed 100% mortality, whereas the silica-coated QD-treated embryos stayed viable and healthy throughout and after the experiments, devoid of any deformities. We provide highly cogent and convincing evidence for such silica-coated QDs as a model nanoparticle in practice, to achieve in vitro and in vivo precision targeted imaging.