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Malignant brain tumors remain a major cause of concern and mortality as successful treatment is hindered due to the poor transport and low penetration of chemotherapeutics across the blood-brain barrier (BBB). In this study, a nano formulation composed of chlorotoxin (CTX)-conjugated morusin loaded PLGA nanoparticles (PLGA-MOR-CTX) was devised against Glioblastoma Multiforme (GBM) and its anti-proliferative effects were evaluated in vitro. The synthesized nanoparticles were loaded with morusin, a naturally derived chemotherapeutic drug, and surface conjugated with CTX, a peptide derived from scorpion venom, highly specific for chloride channels (CIC-3) expressed in glioma tumor cells, as well as for matrix metalloproteinase (MMP-2), which is up regulated in the tumor microenvironment. Subsequently, the anti-cancer potential of the NPs was assessed in U87 and GI-1 (human glioblastoma) cells. Antiproliferative, cell apoptosis, and other cell-based assays demonstrated that the PLGA-MOR-CTX NPs resulted in enhanced inhibitory effects on U87 and GI-1 glioma cells. Prominent cytotoxicity parameters such as ROS generation, enhanced caspase activity, cytoskeletal destabilization, and inhibition of MMP-activity were observed in glioblastoma cells upon PLGA-MOR-CTX NP treatment. The cytocompatibility observed with normal human neuronal cells (HCN-1A) and the enhanced lethal effects in glioblastoma cells highlight the potential of PLGA-MOR-CTX nanoparticles as promising therapeutic nanocarriers towards GBM.

Atherosclerosis is Caesar’s sword, which poses a huge risk to the present generation. Understanding the atherosclerotic disease cycle would allow ensuring improved diagnosis, better care, and treatment. Unfortunately, a highly effective and safe way of treating atherosclerosis in the medical community remains a continuous challenge. Conventional treatments have shown considerable success, but have some adverse effects on the human body. Natural derived medications or nutraceuticals have gained immense popularity in the treatment of atherosclerosis due to their decreased side effects and toxicity-related issues. In hindsight, the contribution of nutraceuticals in imparting enhanced clinical efficacy against atherosclerosis warrants more experimental evidence. On the other hand, nanotechnology and drug delivery systems (DDS) have revolutionized the way therapeutics are performed and researchers have been constantly exploring the positive effects that DDS brings to the field of therapeutic techniques. It could be as exciting as ever to apply nano-mediated delivery of nutraceuticals as an additional strategy to target the atherosclerotic sites boasting high therapeutic efficiency of the nutraceuticals and fewer side effects.

Heat Shock Protein 90 (Hsp90) has been extensively explored as a potential drug target for cancer therapies. 17- N-allylamino- 17-demethoxygeldanamycin (17AAG) was the first Hsp90 inhibitor to enter clinical trials for cancer therapy. However, native drug is being shown to have considerable anticancer efficacy against pancreatic cancer when used in combination therapy regime. Further, magnetic hyperthermia has shown to have promising effects against pancreatic cancer in combination with known cyto-toxic drugs under both target and non-targeted scenarios. Hence, in order to enhance the efficacy of 17AAG against pancreatic cancer, we developed poly (lactic-co-glycolic acid) (PLGA) coated, 17AAG and Fe3O4 loaded magnetic nanoparticle formulations by varying the relative concentration of polymer. We found that polymer concentration affects the magnetic strength and physicochemical properties of formulation. We were also able to see that our aqueous dispensable formulations were able to provide anti-pancreatic cancer activity for MIA PaCa-2 cell line in dose and time dependent manner in comparison to mice fibroblast cell lines (L929). Moreover, the in-vitro magnetic hyperthermia against MIA PaCa-2 provided proof principle that our 2-in-1 particles may work against cancer cell lines effectively. Refereed/Peer-reviewed

Suboptimal chemotherapy of anticancer drugs may be attributed to a variety of cellular mechanisms, which synergize to dodge the drug responses. Nearly 2 decades of heat-shock protein 90 (Hsp90)-targeted drug discovery has shown that the mono-therapy with Hsp90 inhibitors seems to be relatively ineffective compared with combination treatment due to several cellular dodging mechanisms. In this article, we have tried to analyze and review the Hsp90 and mammalian target of rapamycin (m-TOR)-mediated drug resistance mechanisms. By using this information we have discussed about the rationale behind use of drug combinations that includes both or any one of these inhibitors for cancer therapy. Currently, biodegradable nano vector (NV)-loaded novel drug delivery systems have shown to resolve the problems of poor bioavailability. NVs of drugs such as paclitaxel, doxorubicin, daunorubicin, and others have been successfully introduced for medicinal use. Hence, looking at the success of NVs, in this article we have also discussed the progress made in the delivery of biodegradable NV-loaded Hsp90 and m-TOR-targeted inhibitors in multiple drug combinations. We have also discussed the possible ways by which the market success of biodegradable NVs can positively impact the clinical trials of anti-Hsp90 and m-TOR combination strategy. Refereed/Peer-reviewed

Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicity and resistivity in the long run. A nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicity. GANT61 and curcumin were co-delivered via polymeric nanoparticles (NPs) for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single-emulsion-solvent evaporation method for the preparation of the therapeutic NPs. The GANT61-curcumin PLGA NPs were characterized for their size, shape and chemical properties, and anti-cancer cell studies were undertaken for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The NPs induced cytotoxic effects in breast cancer cells at a mid-minimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual-drug NPs thus provide a novel perspective on aiding existing anti-cancer nanomedicine therapies to target a heterogeneous tumor mass effectively.

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.

Polysaccharides that show finest bioactivities and physicochemical properties are always promising for bionanoscience applications. Mauran is such a macromolecule extracted from halophilic bacterium, Halomonas maura for biotechnology and nanoscience applications. Antioxidant properties of MR/CH nanoparticles were studied using biochemical assays to prove the versatility of these test nanoparticles for biomedical applications. Here, we demonstrate the prospects of extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded MR/CH nanoparticles were tested for anticancer proliferation and compared their therapeutic efficiency using breast adenocarcinoma and glioma cells. Fluorescently labeled nanoparticles were employed to show the cellular uptake of these nanocarriers using confocal microscopic imaging and flow cytometry.

Introduction of a novel biocompatible, stable, biomaterial for drug delivery application remains always challenging. In the present study, we report the synthesis of an extremophilic bacterial sulfated polysaccharide based nanoparticle as a stable biocompatible material for drug delivery, evaluation of anticancer efficacy and bioimaging. Mauran (MR), the sulfated exopolysaccharide extracted from a moderately halophilic bacterium, Halomonas maura was used for the synthesis of nanoparticles along with chitosan (CH). MR/CH nanoparticles were synthesized by simple polyelectrolyte complexation of anionic MR and cationic CH. The MR/CH hybrid nanoparticles formed were ranging between 30 and 200 nm in diameter with an overall positive zeta potential of 27.5±5 mV and was found to be stable under storage in solution for at least 8 weeks. In vitro drug release studies showed a sustained and prolonged delivery of 5-fluorouracil (5FU) for 10-12 days from MR/CH nanoparticles under three different pHs of 4.5, 6.9 and 7.4 respectively. Cytotoxicity assay revealed that MR/CH nanoparticles were non-cytotoxic towards normal cells and toxic to cancer cells. Also, 5FU loaded MR/CH nanoparticles were found more effective than free 5FU in its sustained and controlled manner of killing breast adenocarcinoma cells. Fluorescein isothiocyanate (FITC) labeled MR/CH nanoparticles were used for cell binding and uptake studies; thereby demonstrating the application of dye tagged MR/CH nanoparticles for safe and nontoxic mode of live cellular imaging. We report the introduction of an extremophilic bacterial polysaccharide, MR, for the first time as a novel biocompatible and stable biomaterial to the world of nanotechnology, pharmaceutics and biomedical technology.

A 'green' synthesis for encapsulating PbSe nanoparticles with soluble starch at room temperature has been demonstrated. The structural and thermal properties of the nanoparticles have been investigated. TEM micrographs showed that the particles were cubical to spheroid in shape and the average size of the particles was 25 nm. The starch coating onto the nanoparticles did not affect the morphology of the cells in our in vitro studies indicating the coating was biocompatible and nontoxic. Our cytotoxicity studies showed that the biocompatibility was enhanced when the nanoparticles were coated with starch and PbSe starch nanoparticles could provide greater cell viability even at particle loading as high as 100 μg/ml. Refereed/Peer-reviewed

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. Biotechnol. Bioeng. 2012; 109: 2920–2931. © 2012 Wiley Periodicals, Inc.

CdTe/CdSe quantum dots (QDs) embedded gelatin nanoparticles were synthesized via aqueous method. The morphology of the nanoparticles was characterized by transmission electron microscope (TEM) and the average size of QD/gelatin nanoparticles was 50 nm in size. The luminescent properties of these nanoparticles were studied by using fluorescence spectrophotometry and fluorescence microscopy. The nanoparticles was used for imaging cell lines such as GI-1, MCF 7, HUVEC, L929 and biocompatibility of nanoparticles was studied and found that the gelatin coated QDs are highly compatible even at higher concentrations of nanoparticles. Our results identify that biopolymer coated nanoparticles are expected to be ideal candidates for in vivo biological imaging studies. © 2011 by American Scientific Publishers All rights reserved. Refereed/Peer-reviewed

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.

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.

Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10-and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others. Refereed/Peer-reviewed

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.

Alzheimer's disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimer's disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimer's disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimer's disease proving it to be a potential therapeutic tool against this dreaded disease.

The use of fluorescent nanomaterials with good photostability and biocompatibility in live imaging of cells has gained increased attention. Even though several imaging techniques have been reported for mammalian cells, very limited literatures are available for nanomaterial based live imaging in plant system. We studied the uptake ability of two different nanomaterials, the highly photostable CdSe quantum dots and highly biocompatible FITC-labeled silica nanoparticles by rice seedlings which could provide greater opportunities for developing novel in vivo imaging techniques in plants. The effects of these nanomaterials on rice seed germination have also been studied for analyzing their phytotoxic effects on plants. We observed good germination of seeds in the presence of FITC-labeled silica nanoparticles whereas germination was arrested with quantum dots. The uptake of both the nanomaterials has been observed with rice seedlings, which calls for more research for recommending their safe use as biolabels in plants.

Nano Drug Delivery, as a treatment method against brain tumors, is a progressing area in the field of precise targeted drug administration methodology. The unresolved problems related to chemotherapy, other invasive therapeutic procedures and various obstructions offered by biological barriers are circumvented by nanodrug delivery. Recent dramatic developments in nanotechnology have created a lot of nano-devices which could be used against cancer. Infiltration, modulation of the Blood Brain Barrier, camouflaged from immune defense mechanism and the specific targeting of cancer affected cells are a few of the attractive features of nanodevices. We present here a review of newly evolved nanoplatforms in brain tumor therapy in which careful attention has been paid into various form nanoparticles, useful targeting ligands, altered chemotherapy agents and existing tumor therapy methods using nanotechnology.

Srivani Veeranarayanan, Aby Cheruvathoor Poulose, M Sheikh Mohamed, Yutaka Nagaoka, Seiki Iwai, Yuya Nakagame, Shosaku Kashiwada, Yasuhiko Yoshida, Toru Maekawa, D Sakthi KumarBio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, JapanAbstract: 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.Keywords: endothelial imaging, CD31, silica nanoparticle, CdS QDs, medaka embryos, biocompatibility