Nanomedicine

The focus of research in our laboratory is to explore biomedical applications of nanotechnology. Nanoparticles and nanomaterials offer potential benefit in wide range of applications such as in sensing, diagnostics, delivery and image enhancement.


Fibronectin and Vitronectin Promote Human Fetal Osteoblast Cell Attachment and Proliferation on Nanoporous Titanium Surfaces,  J. Biomed. Nanotechnol. V.9, p.1092-1097 (2013) 

We studied the influence of the serum proteins fibronectin (FN) and vitronectin (VN) with nanoporous TiO2 on osteoblast cell attachment. Taken together, these results suggest that the nanoporous surface topography results in increased  adsorbtion of FN and VN the slow release of these proteins are important factors in osteoblast attachment to titanium alloys.


In vitro evaluation of theranostic polymeric micelles for imaging and drug delivery in cancer, Theranostics 2012, V.doi:10.7150, P.thno.3927 (2012)   

We describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.


In vitro radiosensitization by gold nanoparticles during continuous low dose rate gamma irradiation with I-125 brachytherapy seeds , Nanomedicine-Nanotechnology Biology And Medicine v.9, p.257 (2013)  

This communication reports the first experimental evidence of gold nanoparticle (AuNP) radiosensitization during continuous low-dose-rate (LDR) gamma irradiation with low-energy brachytherapy sources.


Thermomagnetic determination of Fe3O4 magnetic nanoparticle diameters for biomedical applications
Journal of Magnetism and Magnetic Materials, V.Vol. 323,, P.P. 2310-2317 (2011)

In this work the average particle diameter and distribution of an ensemble of Fe3O4 ferrimagnetic nanoparticles are determined solely from temperature-dependent magnetization measurements.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.


Optimal drug release schedule for in-situ radiosensitization of image guided permanent prostate implants,  Proc. SPIE, V.7964, P.79640A (2011)  

This work determines the optimal elution schedules for 125I prostate brachytherapy. The interaction between  brachytherapy dose distributions and drug distribution around drug eluting spacers is modeled using a linear-quadratic (LQ)  model of cell kill. Making brachytherapy spacers from radiosensitizer eluting polymer transforms inert parts of the implant process into a means of enhancing the effect of the brachytherapy radiation.  Such an approach may increase the therapeutic ratio of prostate brachytherapy or offer a means of locally boosting the radiation effect without increasing the radiation dose to surrounding tissues.


Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT), Phys Med Biol, V.55(20), P.6039-52 (2010)  

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.  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.


Biological In Situ Dose-painting for Image-guided Radiation Therapy using Drug-loaded Implantable Devices, International Journal of Radiation Oncology * Biology * Physics , V.76, P.615-623 (2010)

Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting


Monitoring of magnetic targeting to tumor vasculature through MRI and biodistribution

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.


Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)

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).


Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices

The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al2O3), titanium oxide (TiO2) and porous silicon are highlighted with illustrative examples.


Sustained Drug Release from Non-eroding Nanoporous Templates

We present the results for the release of a model drug, doxorubicin (Dox), fromdifferent non-eroding nanopor- ous coatings. Detailed studies of drug release from these platforms in the form of anodic aluminum oxide (AAO) and anodic titaniumoxide (ATO)were carried out.


Chitosan Film Containing Poly(D,L-Lactic-Co-Glycolic Acid)Nanoparticles: A Platform for Localized Dual-Drug Release

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.


Biological In Situ Dose Painting For Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices (BIS-IGRT)

Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio.We model this new approach for two types of treatment.


A new paradigm in diagnostics and therapy

The focus of research in our laboratory is to explore biomedical applications of nanotechnology. Nanoparticles and nanomaterials offer potential benefit in wide range of applications such as in sensing, diagnostics, delivery and image enhancement.


Magnetic nanoparticles as MRI contrast enhancement agent

Magnetic nanoparticles in the form of superparamagnetic iron oxide nanoparticles are increasingly being used as contrast enhancement agent in magnetic resonance imaging (MRI). Our approach is through micelle-based nanotechnology platform.


Nanoporous alumina and titania templates for drug/gene delivery

New generations of biomedical implants and cardiovascular stents that are currently being used have the property of localized elution of drug molecules to enhance lifetime of these devices and for bio-integration. In this project Sridhar group is using nanoporous alumina and titania coatings for localized drug and gene delivery applications.


High-throughput Assembly of Nanoelements in Nanoporous Alumina Templates

We 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 vitro imaging of embryonic stem cells using multiphoton luminescence of gold nanoparticles

We demonstrate in vitro imaging using multi-photon photoluminescence of gold nanoparticles from two different cell types - Dictyostelium discoideum and mouse embryonic stem cells.


Surface Functionalization of Gold Nanoparticles using Hetero-Bifunctional Poly (Ethylene Glycol) Spacer for Intracellular Tracking and Delivery

For development of surface functionalized gold nanoparticles as cellular probes and delivery agents, we have synthesized hetero-bifunctional polyethylene glycol (PEG, MW 1,500) having a thiol group on one terminus and a reactive functional group on the other for use as a flexible spacer.


Metallic Nanoparticles for Multi-Modal Imaging of Skin Cancer

We show that the optical properties of noble-metal 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.


Biological in-situ dose-painting for image-guided radiation therapy using drug-loaded implantable devices

Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments, such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically-active drugs, providing an opportunity to enhance the therapeutic ratio.

Sustained Drug Release from Non-eroding Nanoporous Templates

We demonstrate that the nanoporous platforms can be used as non-eroding sustained release systems which can be utilized as coatings on currently available implants such as cardio-vascular stents, orthopedic/dental implants, fiducials or spacers.


Functionalization-induced improvement in magnetic properties of Fe3O4 nanoparticles for biomedical applications

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. SQUID magnetometry confirmed superparamagnetic behavior in the nanoparticles.


Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles

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.

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