12 results on '"Lee, Robert J."'
Search Results
2. A novel strategy for controlled synthesis of transferrin-conjugated lipid nanoparticles by a microfluidic device.
- Author
-
Li, Yujing, Lee, Robert J., Li, Yuhuan, Sun, Yating, Huang, Xueqin, Xie, Jing, and Teng, Lesheng
- Subjects
- *
LIPIDS , *TRANSFERRIN , *NANOPARTICLES , *MICROFLUIDIC devices , *SMALL interfering RNA - Published
- 2017
- Full Text
- View/download PDF
3. Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin®) conjugated polyethylenimine
- Author
-
Chiu, Shih-Jiuan, Ueno, Naoto T., and Lee, Robert J.
- Subjects
- *
GENE therapy , *TRASTUZUMAB , *ANTINEOPLASTIC agents , *CANCER treatment - Abstract
A series of novel nonviral vectors targeting the HER-2/neu gene product human epidermal growth factor receptor-2 (HER2) were constructed and evaluated in breast cancer cell lines to optimize vector formulation for receptor-specific gene transfer. These vectors were DNA/polycation complexes (polyplexes) prepared by mixing, at varying ratios, plasmid DNA carrying a luciferase reporter gene to HerPEI, which is a conjugate of linear polyethylenimine (PEI), a cationic polymer, and trastuzumab (Herceptin®), a HER2-specific monoclonal antibody. Transfection studies were carried out in both HER2 overexpressing Sk-Br-3 and HER2 low-expressing MDA-MB-231 breast cancer cells. The HerPEI polyplexes showed significantly greater transfection activity up to 20-folds than nonderivatized PEI-based polyplexes in the Sk-Br-3 cells. The transfection efficiency of targeted polyplexes was dependent on the trastuzumab:PEI ratio and can be blocked by excess free trastuzumab, suggesting HER2-mediated gene delivery. In contrast, no significant difference in transfection activities was observed between HER2-targeted and nontargeted polyplexes in the HER2 low-expressing MDA-MB-231 cells. The transfection efficiency of HerPEI polyplexes was retained in serum-containing medium. In summary, HerPEI polyplexes have shown promising HER2 receptor-specific gene transfer properties and warrant further evaluation as a tumor-targeted vector for gene therapy. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
4. Characterization of a novel diolein-based LPDII vector for gene delivery
- Author
-
Guo, Wenjin, Gosselin, Michael A., and Lee, Robert J.
- Subjects
- *
GENE therapy , *LIPOSOMES - Abstract
LPDII vectors are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA (polyplexes) complexed with anionic pH-sensitive liposomes. Here, we describe a novel LPDII formulation containing polyethylenimine (PEI) polyplexes complexed with anionic pH-sensitive liposomes composed of diolein/cholesteryl hemisuccinate (CHEMS) (6:4 mol/mol). The pH-sensitivity of diolein/CHEMS liposomes was evaluated through quantitative fluorescence measurements of calcein release and particle size analysis. The results indicated that diolein/CHEMS liposomes are stable at physiological pH, but undergo rapid aggregation and fluorescence dequenching at pH values ≤5.0. Using a luciferase reporter gene, in vitro transfection of KB oral cancer cells showed that the transfection efficiency of LPDII vectors was superior to other well-characterized polyplexes and lipoplexes. Results further showed that gene delivery using diolein-containing LPDII vectors was dependent on the PEI nitrogen/DNA phosphate (N/P) ratio, the lipid/DNA weight ratio and the cell line being transfected. Replacing PEI with poly-l-lysine as the DNA condensing agent resulted in only a moderate reduction in transfection activity. Moreover, in contrast to LPDII formulations incorporating dioleoylphosphatidylethanolamine (DOPE), the transfection efficiency of diolein-based LPDII vectors was sustained in media containing up to 50% fetal bovine serum. Since diolein-based LPDII vectors mediate efficient gene transfer and retain their transfection activity in the presence of serum, diolein may be a promising alternative to DOPE for the construction of non-viral vectors for in vivo gene delivery. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
5. Skin cancer treatment effectiveness is improved by iontophoresis of EGFR-targeted liposomes containing 5-FU compared with subcutaneous injection.
- Author
-
Petrilli, Raquel, Eloy, Josimar O., Saggioro, Fabiano P., Chesca, Deise L., de Souza, Marina Claro, Dias, Marcos V.S., daSilva, Luis L.P., Lee, Robert J., and Lopez, Renata F.V.
- Subjects
- *
CANCER treatment , *SKIN cancer , *IONTOPHORESIS , *EPIDERMAL growth factor receptors , *LIPOSOMES , *SQUAMOUS cell carcinoma , *GENETIC overexpression - Abstract
Squamous cell carcinoma (SCC) is a malignant tumor in which epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis and malignancy. For SCC treatment, cetuximab, an anti-EGFR antibody, is administered in combination with a chemotherapeutic drug for improved efficacy. In this work, an EGFR-targeted immunoliposome loaded with 5-fluorouracil (5- FU) was developed to allow co-administration of the antibody and the chemotherapeutic agent and selective delivery to SCC cells. Topically applied iontophoresis and subcutaneous injections of the 5-FU-loaded immunoliposomes were employed in an SCC xenograft animal model to evaluate the influence of the administration route on therapeutic efficacy. In vitro, cellular uptake of cetuximab-immunoliposomes by EGFR-positive SCC cells was 3.5-fold greater than the uptake of control liposomes. Skin penetration studies showed that iontophoresis of immunoliposomes doubled the 5-FU penetration into the viable epidermis compared with the same treatment with control liposomes. In vivo, subcutaneous injection of immunoliposomes reduced tumor volume by >60% compared with the negative control and approximately 50% compared with the 5-FU solution and control liposome treatments. Interestingly, topical administration via iontophoresis improved tumor reduction by almost 2-fold compared with subcutaneous administration of 5-FU solution and control liposomes but was equally effective for the immunoliposome treatment. However, histological analysis showed that iontophoresis of immunoliposomes was more effective than subcutaneous injection in reducing cell proliferation, resulting in cells with less aggressive characteristics. In conclusion, topical administration of immunoliposomes containing 5-FU using iontophoresis is a promising strategy for SCC treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
6. Functional exosome-mimic for delivery of siRNA to cancer: in vitro and in vivo evaluation.
- Author
-
Yang, Zhaogang, Xie, Jing, Zhu, Jing, Kang, Chen, Chiang, Chiling, Wang, Xinmei, Wang, Xiaobing, Kuang, Tairong, Chen, Feng, Chen, Zhou, Zhang, Aili, Yu, Bo, Lee, Robert J., Teng, Lesheng, and Lee, L. James
- Subjects
- *
SMALL interfering RNA , *CANCER diagnosis , *DRUG delivery systems , *PHARMACEUTICAL technology , *GENE delivery techniques - Abstract
Exosomes, the smallest subgroup of extracellular vesicles, have been recognized as extracellular organelles that contain genetic and proteomic information for long distance intercellular communication. Exosome-based drug delivery is currently a subject of intensive research. Here, we report a novel strategy to produce nanoscale exosome-mimics (EMs) in sufficient quantity for gene delivery in cancer both in vitro and in vivo . Size-controllable EMs were generated at a high yield by serial extrusion of non-tumorigenic epithelial MCF-10A cells through filters with different pore sizes. siRNA was then encapsulated into the EMs by electroporation. Biosafety and uptake efficiency of the EMs were evaluated both in vitro and in vivo . The mechanism underlying their cellular endocytosis was also studied. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
7. Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid nanoparticle formulations.
- Author
-
Wang, Xinmei, Yu, Bo, Ren, Wei, Mo, Xiaokui, Zhou, Chenguang, He, Hongyan, Jia, HuLiang, Wang, Lu, Jacob, Samson T., Lee, Robert J., Ghoshal, Kalpana, and Lee, L. James
- Subjects
- *
DRUG delivery systems , *SMALL interfering RNA , *MICRORNA , *OLEIC acid , *NANOMEDICINE , *LIVER disease treatment , *DRUG development - Abstract
Abstract: Many cationic lipids have been developed for lipid-based nanoparticles (LNPs) for delivery of siRNA and microRNA (miRNA). However, less attention has been paid to “helper lipids”. Here, we investigated several “helper lipids” and examined their effects on the physicochemical properties such as particle size and zeta potential, as well as cellular uptake and transfection efficiency. We found that inclusion of oleic acid (OA), an unsaturated fatty acid, into the LNP formulation significantly enhanced the delivery efficacy for siRNA and miRNA. For proof-of-concept, miR-122, a liver-specific microRNA associated with many liver diseases, was used as a model agent to demonstrate the hepatic delivery efficacy both in tumor cells and in animals. Compared to Lipofectamine 2000, a commercial transfection agent, LNPs containing OA delivered microRNA-122 in a more efficient manner with a 1.8-fold increase in mature miR-122 expression and a 20% decrease in Bcl-w, a target of microRNA-122. In comparison with Invivofectamine, a commercial transfection agent specifically designed for hepatic delivery, LNPs containing OA showed comparable liver accumulation and in vivo delivery efficiency. These findings demonstrated the importance of “helper lipid” components of the LNP formulation on the cellular uptake and transfection activity of siRNA and miRNA. LNPs containing OA is a promising nanocarrier system for the delivery of RNA-based therapeutics in liver diseases. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
8. Lactosylated gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma.
- Author
-
Zhang, Mengzi, Zhou, Xiaoju, Wang, Bo, Yung, Bryant C., Lee, Ly J., Ghoshal, Kalpana, and Lee, Robert J.
- Subjects
- *
GRAMICIDINS , *NANOMEDICINE , *LIPIDS , *TARGETED drug delivery , *DRUG delivery systems , *LIVER cancer , *MICRORNA - Abstract
Abstract: Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73nm, zeta potential of +3.5mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPβ and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPβ and FOXP3 by 6.9- and 2.2-fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
9. Delivery of antisense oligodeoxyribonucleotide lipopolyplex nanoparticles assembled by microfluidic hydrodynamic focusing
- Author
-
Koh, Chee Guan, Zhang, Xulang, Liu, Shujun, Golan, Sharon, Yu, Bo, Yang, Xiaojuan, Guan, Jingjiao, Jin, Yan, Talmon, Yeshayahu, Muthusamy, Natarajan, Chan, Kenneth K, Byrd, John C., Lee, Robert J., Marcucci, Guido, and Lee, L. James
- Subjects
- *
DEOXYRIBONUCLEOTIDES , *NANOPARTICLES , *MICROFLUIDICS , *HYDRODYNAMICS , *MESSENGER RNA , *PROTEINS , *APOPTOSIS , *LIPOSOMES - Abstract
Abstract: A multi-inlet microfluidic hydrodynamic focusing (MF) system to prepare lipopolyplex (LP) containing Bcl-2 antisense deoxyoligonucleotide (ODN) was developed and evaluated. The lipopolyplex nanoparticles consist of ODN:protamine:lipids (1:0.3:12.5wt/wt ratio) and the lipids included DC-Chol:egg PC:PEG–DSPE (40:58:2mol/mol%). Using K562 human erythroleukemia cells, which contain an abundance of Bcl-2 and overexpression of transferrin receptors (TfR), and G3139 (oblimerson sodium or GenasenseTM) as a model cell line and drug, respectively, the Bcl-2 down-regulation at the mRNA and protein levels as well as cellular uptake and apoptosis was compared between the conventional bulk mixing (BM) method and the MF method. The lipopolyplex size and surface charge were characterized by dynamic light scattering (DLS) and zeta potential (ζ) measurement, respectively, while the ODN encapsulation efficiency was determined by gel electrophoresis. Cryogenic transmission electron microscopy (Cryo-TEM) was used to determine the morphology of LPs. Our results demonstrated that MF produced LP nanoparticles had similar structures but smaller size and size distribution compared to BM LP nanoparticles. MF LP nanoparticles had higher level of Bcl-2 antisense uptake and showed more efficient down-regulation of Bcl-2 protein level than BM LP nanoparticles. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
10. Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes
- Author
-
Chiu, Shih-Jiuan, Liu, Shujun, Perrotti, Danilo, Marcucci, Guido, and Lee, Robert J.
- Subjects
- *
LIPOSOMES , *BILAYER lipid membranes , *CYTOPLASM , *BLOOD proteins - Abstract
Abstract: A novel transferrin receptor (TfR)-targeted liposomal formulation was synthesized and evaluated for the delivery of a phosphorothioate antisense oligodeoxyribonucleotide (ODN) (G3139, oblimerson sodium, or Genasense™) to Bcl-2 in K562 leukemia cells. Liposomes composed of DC-Chol/egg PC/PEG–DSPE (25:73.5:1.5, mol/mol/mol) were loaded with G3139 with high efficiency (70–80%). To prepare targeted liposomes, transferrin was first coupled to PEG–DSPE and then incorporated into the bilayer by post-insertion. The liposomes had a mean diameter of 100 to 150 nm and exhibited colloidal stability for up to 8 weeks. Uptake of Tf-conjugated G3139-containing liposomes in TfR positive K562 cells was found to be more efficient than that of the non-targeted control formulation and could be blocked by excess free Tf. Treatment with Tf-conjugated liposomes resulted in Bcl-2 protein downregulation in K562 cells that was approximately 2-fold greater than with non-targeted liposomes (p <0.05) and 10-fold greater than with free G3139. Treatment with 2 μM G3139 in Tf-conjugated liposomes resulted in >80% reduction in Bcl-2 transcript. In addition, Tf-conjugated liposomal G3139-sensitized K562 cells to daunorubicin, lowering IC50 from 1.8 μM to 0.18 μM. In conclusion, Tf-conjugated liposomes are effective delivery vehicles for G3139 antisense oligos in TfR positive K562 cells and warrant further investigation as an in vivo oligo delivery vehicle. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
11. Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations
- Author
-
Shi, Guangfeng, Guo, Wenjin, Stephenson, Stacy M., and Lee, Robert J.
- Subjects
- *
LIPOSOMES , *LIPIDS , *DRUG delivery systems - Abstract
pH-sensitive liposomes are designed to promote efficient release of entrapped agents in response to low pH. In this study, novel pH-sensitive liposomes consisting of cationic/anionic lipid combinations are evaluated for intracellular drug and gene delivery. First, liposomes composed of egg phosphatidylcholine, dimethyldioctadecylammonium bromide (DDAB), cholesteryl hemisuccinate (CHEMS), and Tween-80 (25:25:49:1, mol/mol) were shown to stably entrap calcein at pH 7.4 and undergo rapid content release and irreversible aggregation under acidic pH. Compared to pH-sensitive liposomes incorporating dioleoylphosphatidylethanolamine, these liposomes showed improved retention of pH-sensitivity in the presence of serum. The folate receptor (FR), which is amplified in a wide variety of human tumors, could be targeted by incorporating 0.1 mol% folate-polyethyleneglycol-phosphatidylethanolamine (f-PEG-PE) into liposomes. f-PEG-PE has been shown to facilitate FR-mediated endocytosis of liposomes into KB human oral cancer cells, which express amplified FR. FR-targeted pH-sensitive liposomes produced increased cytosolic release of entrapped calcein, as shown by fluorescence microscopy, and enhanced cytotoxicity of entrapped cytosine-β-d-arabinofuranoside, as shown by an 11-fold reduction in the IC50 in KB cells, compared to FR-targeted non-pH-sensitive liposomes. Furthermore, FR-targeted pH-sensitive liposomes composed of DDAB/CHEMS/f-PEG-PE, combined with polylysine-condensed plasmid DNA, were shown to mediate FR-specific delivery of a luciferase reporter gene into KB cells in the presence of 10% serum. These findings suggest that cationic lipid-containing pH-sensitive liposomes, combined with FR targeting, are effective vehicles for intracellular drug and gene delivery. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
12. Efficient antisense oligonucleotide delivery via non-covalent complexes of folic acid and modified polyethylenimine.
- Author
-
Yang, Shuang, Yang, Xuewei, Xie, Jing, Lee, Robert J., and Teng, Lesheng
- Subjects
- *
PTERIDINES , *FOLIC acid , *DRUG delivery systems , *CONTROLLED release technology , *CONTROLLED release drugs , *INDUSTRIAL chemistry - Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.