Publications (6)16.29 Total impact
-
Chapter: Raman Micro-spectral Imaging of Cells and Intracellular Drug Delivery Using Nanocarrier Systems
[show abstract] [hide abstract]
ABSTRACT: Raman spectroscopy in combination with optical microscopy provides a new non-invasive method to examine and image cellular processes. Based on the spectral parameters of a cell’s components it is possible to image cellular organelles, such as the nucleus, chromatin, mitochondria, or lipid bodies, at the resolution of conventional microscopy. Several multivariate or spectral de-mixing algorithms, for example, hierarchical cluster analysis or orthogonal subspace projection, may be used to reconstruct an image of a cell. The non-invasive character of the technique as well as the associated chemical information may offer advantages over other imaging techniques such as fluorescence microscopy. Currently of particular interest are the uptake and intracellular fate of various pharmaceutical nanocarriers, which are widely used for drug delivery purposes, including intracellular drug and gene delivery. We have imaged the uptake and distribution patterns of several carrier systems over time. In order to distinguish the species of interest from their cellular environment spectroscopically, the carrier particles or the drug load itself may be labeled with deuterium. The first part of the chapter will briefly introduce the concept of Raman imaging in combination with multivariate data analysis on some simple cell models, after which the results of the uptake studies are discussed.01/2011: pages 137-163; -
Article: Near infrared planar tumor imaging and quantification using nanosized Alexa 750-labeled phospholipid micelles.
[show abstract] [hide abstract]
ABSTRACT: A novel highly biocompatible near infrared nanosized contrast agent was developed and used for rapid tumor detection and quantification using planar optical imaging and analysis. With this in mind, the near infrared fluorescent dye Alexa 750 was covalently attached to polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate, and double labeled (with Alexa and rhodamine) PEG-PE micelles were injected into mice and observed using planar optical imaging. Pixel intensity data from the tumor site were normalized versus the autofluorescence of the animal at the same time point and normalized as signal to noise over the scattered light from the various tissues of the mice. The detected signal from the tumor was higher than the background noise allowing for rapid detection of the tumor. The tumor was clearly visible within one hour. Some signal was also detected from the abdomen of the mice. As determined by microscopy analysis, other organs of accumulation were the liver and kidney, which corresponded well to the data from the whole body imaging animal studies.International Journal of Nanomedicine 02/2009; 4:123-31. · 3.13 Impact Factor -
Article: Self-assembling micelle-like nanoparticles based on phospholipid-polyethyleneimine conjugates for systemic gene delivery.
[show abstract] [hide abstract]
ABSTRACT: With few exceptions, where local administration is feasible, progress towards broad clinical application of gene therapies requires the development of effective delivery systems. Here we report a novel non-viral gene delivery vector, 'micelle-like nanoparticle' (MNP) suitable for systemic application. MNP were engineered by condensing plasmid DNA with a chemical conjugate of phospholipid with polyethylenimine (PLPEI) and then coating the complexes with an envelope of lipid monolayer additionally containing polyethylene glycol-phosphatidyl ethanolamine (PEG-PE), resulting in spherical 'hard-core' nanoparticles loaded with DNA. MNP allowed for complete protection of the loaded DNA from enzymatic degradation, resistance to salt-induced aggregation, and reduced cytotoxicity. MNP also demonstrated prolonged blood circulation and low RES accumulation. Intravenous injection of MNP loaded with plasmid DNA encoding for the Green Fluorescence Protein (GFP) resulted in an effective transfection of a distal tumor. Thus, MNP provide a promising tool for systemic gene therapy.Journal of Controlled Release 11/2008; 133(2):132-8. · 5.73 Impact Factor -
Article: Photoactivated enediynes as targeted antitumoral agents: efficient routes to antibody and gold nanoparticle conjugates.
[show abstract] [hide abstract]
ABSTRACT: Efficient syntheses of a series of functionalized aryl enediynes have been developed. The building blocks were used to effect conjugation to carrier PEG templates which allowed subsequent coupling to a cardiac targeted monoclonal antibody. Immunocompetence of the enediyne-Mab conjugates was demonstrated by ELISA, and both parent enediynes and bioconjugates underwent successful photo-Bergman cyclization. Finally, surface modified (Au) nanoparticle conjugates were prepared and size confirmed by TEM analysis. Application as long-circulating photoactivated prodrugs is anticipated.Bioorganic & medicinal chemistry letters 03/2008; 18(3):934-7. · 2.65 Impact Factor -
Article: Raman Microscopic Imaging of Cells and Applications Monitoring the Uptake of Drug Delivery Systems
Proc SPIE 01/2008; -
Article: New ways of imaging uptake and intracellular fate of liposomal drug carrier systems inside individual cells, based on Raman microscopy.
[show abstract] [hide abstract]
ABSTRACT: Recent developments, combining Raman spectroscopy with optical microscopy, provide a new noninvasive technique to assess and image cellular processes. Of particular interest are the uptake mechanisms of various cytologically active compounds. In order to distinguish the species of interest from their cellular environment spectroscopically, compounds may be labeled with deuterium. Here, we apply Raman microspectroscopy to follow the uptake of liposomal drug carrier systems that have been introduced to deliver biologically active compounds to their site of action within human breast adenocarcinoma MCF-7 cells. The distribution patterns of liposomes and liposomes surface-modified with a cell-penetrating peptide (TAT-peptide, TATp) have been imaged over time. The spectroscopic information obtained provides a clear evidence for variable rates, as well as different efficiencies of liposome uptake depending on their surface properties. Depending on the experimental setup, the technique may be applied to fixed or living cell organisms.Molecular Pharmaceutics 5(2):287-93. · 4.78 Impact Factor
Top co-authors
Top Journals
Institutions
-
2011
-
Northeastern University
- Department of Chemistry and Chemical Biology
Boston, MA, USA
-
