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Coumarin class of organic compounds consists of 1,2-benzopyrone ring system as a basic parent scaffold. These benzopyrones are subdivided into alpha-benzopyrones and gammabenzopyrones; with coumarin class of compounds belonging to alpha-benzopyrones. Since the last few years, coumarins were synthesized in many of their derivative forms. Their pharmacological, therapeutic and biochemical properties depend upon their pattern of substitution. Coumarins exhibit a wide range of pharmacological activities, which includes anti-diabetic, anti-viral, anti-microbial, anticancer, anti-oxidant, anti-parasitic, anti-helminthic, anti-proliferative, anti-convulsant, anti-inflammatory and antihypertensive activities. Among these properties, the present review article compiles the detailed research findings of coumarins as anti-cancer agents. Research reports reveal that coumarins inhibit human malignant tumor cell lines in vitro and also show anti-proliferative activity against many mammalian tumors in vivo. Clinical trials conducted on these coumarin class of compounds showed promising activity against several types of cancer such as breast cancer, lung cancer, malignant melanoma, prostate cancer and metastatic renal cell carcinoma etc. This review presents a comprehensive and up to date literature survey on coumarins as anti-cancer agents. Furthermore, a detailed overview of various clinical trials conducted on coumarin class of compounds tested for various types of malignancies has been described.

In the present study, a series of coumarin derivatives were designed, synthesized and evaluated for their antioxidant and cytotoxic properties. The title compounds, 2-(3-substituted-4-methyl-2-oxo-2H-chromen-7-yloxy)-2-methylpropanoic acid derivatives 5a–5f, were synthesized by base-catalyzed dehydrohalogenative cyclization following Hantzsch synthesis. All the newly synthesized analogues were characterized and established on the basis of mass, 1H NMR, 13C NMR and IR studies. The compounds were evaluated for their in vitro antioxidant activity and found to exhibit substantial activity. The in vitro cytotoxicity was evaluated against MCF-7, MDA-231 (human breast cancer) and HT29 (human colon adenocarcinoma) cell lines by MTT assay and the results were encouraging. Compound 5b, with lower IC50 values of 2.4 and 4.8 μM for MCF-7 and MDA-231, respectively, was considered to be potent among the series.

Introduction Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo. Methods We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with 59 Fe, 14 C-oleic acid, and 111 In. Results Mouse biodistributions showed 111 In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59 Fe than 111 In in liver and spleen, but lower levels of 14 C. Conclusions While there is some degree of dissociation between the 111 In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component.

Interest in theranostic agents has continued to grow because of their promise for simultaneous cancer detection and therapy. A platform-based nanosized combination agent suitable for the enhanced diagnosis and treatment of cancer was prepared using polymeric polyethylene glycol-phosphatidylethanolamine-based micelles loaded with both, poorly soluble chemotherapeutic agent paclitaxel and hydrophobic superparamagnetic iron oxide nanoparticles (SPION), a Magnetic Resonance Imaging contrast agent. The co-loaded paclitaxel and SPION did not affect each other's functional properties in vitro. In vivo, the resulting paclitaxel-SPION-co-loaded PEG-PE micelles retained their Magnetic Resonance contrast properties and apoptotic activity in breast and melanoma tumor mouse models. Such theranostic systems are likely to play a significant role in the combined diagnosis and therapy that leads to a more personalized and effective form of treatment.

The clinical application of gene silencing mediated by small interfering RNA (siRNA) has been limited by the lack of efficient and safe carriers. Phospholipid modification of low molecular weight polyethylenimine (PEI 1.8 kDa) dramatically increased its gene down-regulation capacity while keeping cytotoxicity levels low. The silencing efficacy was highly dependent on the nature of the lipid grafted to PEI and the polymer/siRNA ratio employed. Phosphoethanolamine (DOPE and DPPE) and phosphocholine (PC) conjugation did not change the physicochemical properties and siRNA binding capacity of PEI complexes but had a large impact on their transfection and ability to down-regulate Green Fluorescent Protein (GFP) expression (60%, 30% and 5% decrease of GFP expression respectively). We found that the micelle-forming structure of DOPE and DPPE-PEI dramatically changed PEI's interaction with cell membranes and played a key role in promoting PEI 1.8 kDa transfection, completely ineffective in the absence of the lipid modification. From the Clinical Editor While siRNA-based gene silencing methods could have numerous clinical applications, efficient delivery remains a major challenge. This team reports that DOPE-PEI and DPPE-PEI based micelle-forming nanostructures may be able to provide an efficient vector for siRNA transfection.

For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of

The utility and promise of magnetic nanoparticles (MagNPs) for biomedicine rely heavily on accurate determination of the particle diameter attributes. While the average functional size and size distribution of the magnetic nanoparticles directly impact the implementation and optimization of nanobiotechnology applications in which they are employed, the determination of these attributes using electron microscopy techniques can be time-consuming and misrepresentative of the full nanoparticle population. In this work the average particle diameter and distribution of an ensemble of Fe 3 O 4 ferrimagnetic nanoparticles are determined solely from temperature-dependent magnetization measurements; the results compare favorably to those obtained from extensive electron microscopy observations. The attributes of a population of biocompatible Fe 3 O 4 nanoparticles synthesized by a thermal decomposition method are obtained from quantitative evaluation of a model that incorporates the distribution of superparamagnetic blocking temperatures represented through thermomagnetization data. The average size and size distributions are determined from magnetization data via temperature-dependent zero-field-cooled magnetization. The current work is unique from existing approaches based on magnetic measurement for the characterization of a nanoparticle ensemble as it provides both the average particle size as well as the particle size distribution.

Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.

To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release.Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS).Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days.The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.

Stable 30–50 nm polymeric polyethylene glycol–phosphatidylethanolamine (PEG–PE)-based micelles entrapping superparamagnetic iron oxide nanoparticles (SPION) have been prepared. At similar concentrations of SPION, the SPION-micelles had significantly better magnetic resonance imaging (MRI) T2 relaxation signal compared to ‘plain’ SPION. Freeze-fracture electron microscopy confirmed SPION entrapment in the lipid core of the PEG–PE micelles. To enhance the targeting capability of these micelles, their surface was modified with the cancer cell-specific anti-nucleosome monoclonal antibody 2C5 (mAb 2C5). Such mAb 2C5-SPION immunomicelles demonstrated specific binding with cancer cells in vitro and were able to bring more SPION to the cancer cells thus demonstrating the potential to be used as targeted MRI contrast agents for tumor imaging.

Improvements in osteoconduction of implant biomaterials require focusing on the bone-implant interface, which is a complex multifactorial system. Surface topography of implants plays a crucial role at this interface. Nanostructured surfaces have been shown to promote serum protein adsorption and osteoblast adhesion when compared to micro-structured surfaces for bone-implant materials. We studied the influence of the serum proteins fibronectin and vitronectin on the attachment and proliferation of osteoblasts onto nanostructured titania surfaces. Human fetal osteoblastic cells hFOB 1.19 were used as model osteoblasts and were grown on nanoporous TiO2 templates, using Ti6AI4V and commercially pure Ti substrates as controls. Results show a significant increase in cell proliferation'on nanoporous TiO2 over flat substrates. Initial cell attachment data exhibited a significant effect by either fibronectin or vitronectin on cell adhesion at the surface of any of the tested materials. In addition, the extent of cell adhesion was significantly different between the nanoporous TiO2 and both Ti6AI4V and commercially pure Ti substrates, with the first showing the highest surface coverage. There was no significant difference on osteoblast attachment or proliferation between the presence of fibronectin or vitronectin using any of the material substrates. Taken together, these results suggest that the increase in osteoblast attachment and proliferation shown on the nanoporous TiO2 is due to an increase in the adsorption of fibronectin and vitronectin because of the higher surface area and to an enhanced protein unfolding, which allows access to osteoblast binding motifs within these proteins.

The advent of nanotechnology has bolstered a variety of nanoparticle-based platforms for different biomedical applications. A better understanding for engineering novel nanoparticles for applications in cancer staging and therapy requires careful assessment of the nanoparticle’s physico-chemical properties. Herein we report a facile synthesis method for PEGylated PLGA nanoparticles encapsulating anti-cancer drug doxorubicin for cancer imaging and therapy. The simple nanoprecipitation method reported here resulted in very robust PEGylated PLGA nanoparticles with close to 95 % drug encapsulation efficiency. The nanoparticles showed a size of ~110 nm as characterized by TEM and DLS. The nanoparticles were further characterized by optical UV–Visible and fluorescence spectroscopy. The encapsulated doxorubicin showed a sustained release (>80 %) from the nanoparticles matrix over a period of 8 days. The drug delivery efficiency of the nanoparticles was confirmed in vitro confocal imaging with PC3 and HeLa cell lines. In vitro quantitative estimation of drug accumulation in PC3 cell line showed a 22 times higher concentration of drug in case of nanoparticle-based formulation in comparison to free drug and this was further reflected in the in vitro cytotoxicity assays. Overall the synthesis method reported here provides a simple and robust PLGA-based platform for efficient drug delivery and imaging of cancer cells in vitro and in vivo.

Aims: The development of noninvasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. The aim of the present study is to show that magnetic cationic liposomes (MCLs), incorporating superparamagnetic iron oxide nanoparticles (SPIONs), are a versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. Materials & methods: MCLs (with incorporated high SPION cargo) were administered to a severe combined immunodeficiency mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre- and post-injection magnetic resonance (MR) images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In-labeled MCLs and the amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. Results: We have shown that tumor signal intensities in T2-weighted MR images decreased by an average of 20 ± 5% and T2* relaxation times decreased by 14 ± 7 ms 24 h after intravenous administration of our MCL formulation. This compares to an average decrease in tumor signal intensity of 57 ± 12% and a T2* relaxation time decrease of 27 ± 8 ms after the same time period with the aid of magnetic guidance. Conclusion: MR and biodistribution analysis clearly show the efficacy of MCLs as MRI contrast agents, prove the use of magnetic guidance, and demonstrate the potential of MCLs as agents for imaging, guidance and therapeutic delivery.

Inthosesituationsitisnecessarytohaveareservoirthatdoesnotdegradeorerode.Non-eroding nanoporousoxide coatingsofferanattractivealternativeplatformsincetheyarenonerodibleandtheir nanofeatures allow control of the elution profile.Herein, we present the results for the release of a modeldrug,doxorubicin(Dox),fromdifferentnon-erodingnanopor-ous coatings. Detailed studies of drug release from theseplatforms in the form of anodic aluminum oxide (AAO) andanodictitaniumoxide(ATO)werecarriedout.Therearemanyapproaches to sputter metals, such as titanium and aluminum,on different materials and to anodize them afterwards

The plasmon resonance conditions in nano-sized materials leads to local field enhancement resulting in amplified response of various linear and nonlinear optical processes at the nano-scale. In this paper, metallic nanoparticles are imaged using several modalities - brightfield, confocal reflectance, two-photon, and second harmonic generation. Two examples are discussed - Au nanoparticles in the zebrafish spinal column, and Ag nanoparticles in fresh skin excisions. We show that the optical properties of noblemetal nanoparticles offer an attractive alternative to the fluorophore-based staining and labeling of biological samples, and have potential use in a wide range of biological and physical applications.

The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al(2)O(3)), titanium oxide (TiO(2)) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution profiles of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release profiles extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved efficacy and integration of implants in a variety of therapeutic situations.

An important feature of nanoparticles is the increased ratio of surface area to volume resulting in large percentage of the atoms on the surface, making them very reactive and offers opportunities to manipulate the properties through these surface atoms. For the most efficient use of nanoparticles in various applications, including biology and medicine, it is important to be able to manipulate the surface chemistry. This paper describes the synthesis and characterization of nanoparticles and the various surface engineering techniques that are utilized for optimizing their applications in nanomedicine.Copyright © 2006 by ASME

Nanotechnology offers unique approaches to probe and control a variety of biological and medical processes that occur at nanometer length scales, and is expected to have a revolutionary impact on biology 1 and medicine 2 . Nanomedicine is a new paradigm that seeks to exploit the use of nanotechnology in medicine. Among the various approaches within the nanomedicine paradigm, nanoparticles and nanotemplates offer some unique advantages as sensing, diagnostic, delivery, and image enhancement agents 3,4 . Several varieties of nanoparticles 5 are available: polymeric nanoparticles 6 , metal nanoparticles 7 , liposomes 8 , micelles, quantum dots, dendrimers, magnetic nanoparticles 9 , and nanoassemblies 10,11 . All of these nanoparticles can play a major role in medicine, and especially in diagnosis and therapy of cancer 12,13,14 , cardiovascular diseases, and infectious diseases. To further the application of nanoparticles in disease diagnosis and therapy, it is important that the systems are stable, capable of being functionalized, biocompatible, and directed to specific target sites in the body after systemic administration. In this short review we discuss four areas of research carried out by the Nanomedicine Consortium using nanoparticles and nanotemplates to explore new approaches in nanotechnology for medical diagnosis, imaging and therapy.

Purpose: Image‐guidedradiation treatments routinely utilize radio‐opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be enhanced through simultaneous in‐situ delivery of radiosensitizers, contained within nanoparticles and nanoporouspolymer matrices coatinggold fiducial markers or spacers implanted in the tumor (BIS‐IGRT, Biological In‐Situ Image‐Guided Radiation Therapy). Methods and Materials: Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymercoatings allowed controlled release of molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system, (Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating) and (ii) Poly(D,L‐lactic‐co‐glycolic acid) (PLGA) nanoparticles loaded with Coumarin‐6, a fluorescent model for a hydrophobic drug, in a chitosan matrix applied as gold fiducial coating. Measurements of temporal release kinetics in buffer and spatial release profiles in agarose were carried out using fluorescence spectroscopy. Results: For gold fiducials coated with Doxorubicin in PMMA matrix an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin‐6 loaded nanoparticles from chitosan film on gold fiducials showed that (63±10)% of NPs were released in twenty days, and after that, the release became slower and additional 37% of release was observed after additional twenty‐days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Conclusions: The results show that dosage and rate of release of these radiosenstizers can be precisely tailored to achieve the desired release profile for BIS‐IGRT.

Detection of ultrasmall masses and identification of biological molecules have been made possible as a result of advances in nanotechnology. Development of biosensing tools has significantly contributed to high-throughput diagnosis and analytical sensing exploiting high affinity of biomolecules. MicroCantilever (MC)-based detection has emerged as a promising biosensing tool for offering label-free and cost-effective sensing capabilities. One of the main criteria determining the success of each biosensor is the capability of the sensing platform to operate in aqueous media. Although being characterized with high sensitivity and simplicity, MCs do not provide an effective tool for measurement of marker proteins in liquid media due to large hydrodynamic damping and losses in the surrounding liquid. In this study, we describe two approaches to high sensitivity biomolecular detection using piezoelectric microcantilevers. (i) Immobilized Mass Detection in Air using electro-mechanical resonance: a unique self-se...

During the last 2 decades no new clinical MRI agents have been approved for clinical use. While Gadolinium based agents have been very popular, Gd cannot be used in emerging multi-functional nano platforms that have the potential to be retained in the body leading to severe toxicity. Superparamagnetic iron-oxide nanoparticles (SPIONs) are most attractive as offering a significant alternative that is far less toxic than Gd based agents. They can be incorporated into nanoplatforms combining other therapeutic agents to achieve image guided drug delivery. Conventionally, SPIONs are imaged via T2 and T2* weighted techniques which manifest signal voids for SPION-containing media. This proves to be disadvantageous in most circumstances because of the difficulty in discriminating signal loss from tissue associated partial voluming, perivascular effects, susceptibility artifacts and motion or flow artifacts. The unique combination of SPIONs with ultra-short TE (UTE) imaging has the specific advantages of rendering positive contrast with high SNR and high CNR, since non-SPION containing regions are dramatically dark due to native tissue's comparatively higher T1. With UTE, it may be possible to take advantage of SPION's inherent biocompatibility allowing for incorporation into drug loaded nanoplatforms leading to bright contrast and the possibility of in vivo quantification. Here, we report on a systematic study of positive contrast MR imaging using magnetic nanoplatforms incorporating SPIONs of varying particle size and functionalization. In the first step, nanoparticles of various sizes from 4 nm to 20 nm were synthesized by the thermal decomposition method in organic solvents and then coated with phospholipids containing PEG. The use of PEGylated phospholipid enables water solubility, imparts better dispersity and long circulation in blood stream. This results in a core-shell like morphology with iron oxide nanoparticle forming the core and phospholipid PEG forming the shell. The nanoparticles were characterized for their size and morphology using dynamic light scattering (DLS) and transmission electron microscopy (TEM). UTE was optimized on a Bruker 7T Biospec at the Center for Translational Neuroimaging (CTNI) at Northeastern University. High-contrast images were obtained by modification of various imaging parameters such as TE, TR, flip angle, pulse length, polar under-sampling, bandwidth and FOV/Geometry. The results are compared in vivo with Feraheme and show good promise for this approach to MR nanoparticle imaging. We acknowledge partial support from NSF DGE 0965843, HHS/5U54CA151881-02, and the Electronics Materials Research Institute at Northeastern University. Citation Format: Codi Gharagouzloo, Manasa Jillela, Rajiv Kumar, Dattatri Nagesha, Srinivas Sridhar. Positive contrast imaging of magnetic nanoplatforms for image-guided drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2673. doi:10.1158/1538-7445.AM2013-2673

The overall goal of this project is to develop means to locally radio-sensitize the prostate to enable prostate cancer (PCa) cure with the use of lower radiation doses, thereby leading to less rectal toxicity. This new approach for chemoradiation therapy (CRT), termed Biological In-Situ Image Guided Radiation Therapy BIS-IGRT, involves the coating of spacers routinely used during prostate I-125-based brachytherapy with radiosensitizing drugs (e.g. docetaxel DTX for PCa). This approach provides localized in-situ delivery of the sensitizer to the tumor and avoids the toxicity associated with current systemic delivery of radiosensitizers. BIS-IGRT adds radiosensitization capability to the standard brachytherapy procedure and with minimal additional inconvenience to the patient. Current CRT with adjuvant systemic chemotherapy does not provide the sustained delivery and drug concentration needed for efficient radiosensitization. Thereby BIS-IGRT improves the therapeutic ratio of radiation therapy without introducing additional patient interventions over current brachytherapy procedures. We have established the following: 1. We have shown through modeling that drug distributions can be achieved that can lead to increased efficiency of image-guided brachytherapy (drug-coated spacers) or image guided external beam therapy (drug-coated fiducials). 2. Doxorubicine-coated fiducials (Dox/PLGA-PEG/CHIT) show release characteristics over 40 days in aqueous media, which is tailored to the time scales required for BIS-IGRT. The cytotoxicity of Dox/ PLGA-PEG NP is comparable to that of free Dox, so that there is no reduction of activity upon encapsulation in the NP. 3. Localized bolus injection of dye-loaded PLGA-PEG nanoparticles (NPs) distributes within 24 hours throughout the tumor, indicating that the sustained release from coated brachytherapy spacers has the potential to achieve the desired biological dose-painting of the tumor. BIS-IGRT could proffer radiation oncologists and medical physicists with a new treatment option for substantially enhancing therapeutic ratio and boosting cure rate for the hundreds of thousands of Americans diagnosed with prostate cancer each year. This new treatment approach would be of crucial benefit for patients with local relapse who require salvage radiotherapy but have reached their radiotherapy normal tissue dose limits. BIS-IGRT can still be accompanied by IV administration of chemotherapeutics, particularly for micro-metastasis, so that existing therapeutic approaches are not compromised. In addition BIS-IGRT could potentially become a mainstream treatment for patients newly diagnosed with prostate or other cancers, where radiation therapy is a common treatment modality. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1473. doi:1538-7445.AM2012-1473

We have developed magnetic nano-liposomes (MNL), incorporating superparamagnetic iron oxide nanoparticles (SPION), that are versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MNL are prepared with a formuation of DPPC:DOTAP:CHOL and DOPE-PEG5000. Incorporation of SPIONs results in MNL with mean diameter of 150-250 nm. MNL are easily taken up by B16-F10 melanoma, HUMVEC-D and breast cancer cell lines. They preferentially target the tumor vasculature as shown in a dorsal skin fold chamber using fluorescently labeled MNL. MNL display superparamagnetic response that is essential for magnetic targeting, MR contrast enhancement and magnetic heating. MNL was administrated to SCID mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In labeled MNL and amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. We have shown that tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2-fold greater accumulation by magnetic targeting. 111In radio-labeled MNL have been shown to enable multi-modal imaging in vivo using MRI and SPeCT/CT. The images show that an MNL bolus injected intra-tumorally was retained in the tumor 24 hours after injection. Application of a magnetic field enables redistribution of the MNL in the tumor. These MNL are also responsive to ac magnetic fields applied using a Copper coil at 360 kHz and 170A driving current. Both hyperthermia (upto 45C) and thermo-ablative temperatures upto 90C were achieved in 10 – 30 minutes ex vivo in buffer. The results indicate high efficiency for magnetic heating using MNL (Specific Absorption Rate ∼ 104 W/kg) and demonstrate the capability to couple ac magnetic fields to MNL to achieve any set of temperatures needed for hyperthermia and thermal ablation. To date there are no truly theranostic platforms that have been approved for clinical use that combine targeting, thermal heating and MRI imaging capabilities. Existing FDA approved magnetic nanoparticle formulations like ferridex and ferumoxytol, are optimized for MR imaging, and have not been shown to be usable for thermal therapy.The MNL platform is a novel nanoplatform combining multi-modal imaging capabilities, with magnetic targeting and thermal therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2011-380

Image-guided radiation treatments routinely utilize implantable devices, such as radio-opaque fiducials or brachytherapy spacers, for improved spatial accuracy. We study the hypothesis that the therapeutic efficiency of IGRT can be further enhanced by biological in-situ dose painting (BIS-IGRT) using local delivery of radiosensitizers embedded within nanoparticles and nanoporous polymer matrices coating gold fiducial markers. Biocompatible polymers loaded with model molecules were coated as a thin film on gold fiducials. The nanoporous morphology of the polymer coatings allowed the controlled release of the molecules and nanoparticles. Two experimental approaches were studied: (i) a free drug release system Doxorubicin, a hydrophilic drug in Poly(methyl methacrylate (PMMA) coating and (ii) Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Coumarin-6, a model for a fluorescent hydrophobic drug, in a chitosan matrix applied as fiducial coating. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. For flat gold films and gold fiducials coated with Doxorubicin in PMMA matrix, an initial release of Dox within the first few hours was followed by a sustained release over the course of next 3 months. Release of Dox from within PMMA matrix is dependent on the concentration of Dox, ratio of PMMA/Dox, thickness of PMMA/Dox coating on gold surface. The release profile of coumarin-6 loaded nanoparticles from chitosan film on gold fiducials showed a continuous release of NPs from the coating during forty days. (63±10)% of NPs were released in twenty days. After that, the release became slower and additional 37% of release was observed after twenty-days. Spatial release profiles in an agarose phantom were also measured and compared with release kinetics models. Results show that dosage and rate of release of these radiosensitizers can be precisely tailored to achieve the desired release profile for BIS-IGRT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2674. doi:10.1158/1538-7445.AM2011-2674

Fe3O4 were synthesized nanoparticles by thermal decomposition method with oleic acid as the surfactant, and to make them suitable for aqueous environments, dopamine ligand exchange was carried out on the particles. The nanoparticle size and phase was quantified by transmission electron microscopy (TEM) and x-ray diffraction (XRD), respectively. Superconducting quantum interference device magnetometry confirmed superparamagnetic behavior in both nanoparticles. A surprising and significant increase in the remanence MR, saturation magnetization MS, and blocking temperature TB of the particles was found after dopamine functionalization, even though TEM and XRD studies revealed no change in the particles’ size and/or structure. The results are consistent with an increase in the magnetic size of the nanoparticle core induced by the dopamine ligand exchange process. These effects are tentatively attributed to surface bonding effects that alter the canted magnetic state of the Fe3O4 nanoparticles.

We demonstrate three-dimensional directed assembly of single-wall carbon nanotubes (SWNT) into porous alumina nanotemplates on silicon substrates by means of electrophoresis and dielectrophoresis at ambient temperatures. Assembled SWNT provided an interconnection between the surface and base of the nanotemplate. I-V measurements clearly show that the connection between silicon and SWNT is established inside the templates. This technique is particularly useful for large scale, rapid, 3D assembly of SWNT over centimeter square areas under mild conditions for nanoscale electronics applications.

The authors demonstrate a nanofabrication method utilizing nanoporous alumina templates which involves directed three dimensional assembly of nanoparticles inside the pores by means of an electrophoretic technique. In their demonstration, they have assembled polystyrene nanobeads with diameter of 50nm inside nanopore arrays of height of 250nm and diameter of 80nm. Such a technique is particularly useful for large-scale, rapid assembly of nanoelements for potential device applications.

CdS nanoparticles (NP), 22 A, have been synthesized from cadmium 2-ethylhexanoate in DMSO as a uniformly sized dispersion. After ripening, CdS exhibits a sharp excitonic emission peak at 402 nm, while in freshly prepared dispersions a broad trapped emission at 510 nm dominates. By using one- and two-dimensional NMR spectroscopy, the conformation of the stabilizer adsorbed to the NP has been determined. The long hexyl chain of 2-ethylhexanoate ions spreads over the surface of NP, whereas the short ethyl end is primarily surrounded by DMSO. Surface modification of CdS with nucleophiles such as 4,4-bipyridine, thiophene, trimethylamine, and thiomolybdate anion results in a partial replacement of the stabilizer and reorientation of the hexyl chain away from the surface. The difference in the degree of replacement and/or conformational changes of 2-ethylhexanoate ion depends on the electron donor activity of the modifier.