23 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. Anti-lung cancer effect of paclitaxel solid lipid nanoparticles delivery system with curcumin as co-loading partner in vitro and in vivo.
- Author
-
Chao Pi, Wenmei Zhao, Mingtang Zeng, Jiyuan Yuan, Hongping Shen, Ke Li, Zhilian Su, Zerong Liu, Jie Wen, Xinjie Song, Lee, Robert J., Yumeng Wei, and Ling Zhao
- Subjects
- *
CURCUMIN , *PACLITAXEL , *LIPIDS , *ZETA potential , *NANOPARTICLES , *ANTINEOPLASTIC agents , *LUNG cancer - Abstract
The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully coencapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (-30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CUþPTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PCSLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CUþPTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-jB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo.
- Author
-
Wenmei Zhao, Mingtang Zeng, Ke Li, Chao Pi, Zerong Liu, Chenglin Zhan, Jiyuan Yuan, Zhilian Su, Yuxun Wei, Jie Wen, Fengjuan Pi, Xinjie Song, Lee, Robert J., Yumeng Wei, and Ling Zhao
- Subjects
- *
DRUG delivery systems , *NANOPARTICLES , *SMALL molecules , *CURCUMIN , *NANOMEDICINE , *PHARMACOKINETICS - Abstract
Context: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]-phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. Objective: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. Materials and methods: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. Results: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0-t) of 37.0-fold. Conclusions: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
5. Design of a Novel Nucleus-Targeted NLS-KALA-SA Nanocarrier to Delivery Poorly Water-Soluble Anti-Tumor Drug for Lung Cancer Treatment.
- Author
-
Yan, Chengyun, Shi, Weiguo, Gu, Jiwei, Lee, Robert J., and Zhang, Yuan
- Subjects
- *
PACLITAXEL , *ANTINEOPLASTIC agents , *LUNG cancer , *CANCER treatment , *WESTERN immunoblotting , *ZETA potential , *CELL nuclei - Abstract
In this study, we designed a novel nucleus-targeted nanocarrier (NLS-KALA-SA, NKSN) consisting of Kala peptide (KALA), nuclear localization signal (NLS) and stearic acid (SA) using Fmoc solid phase synthesis method. We chose Curcumin (CUR), Paclitaxel (PTX), Ginsenoside compound K(CK) as models of poorly water-soluble antitumor drugs, The drugs loaded NLS-KALA-SA nanoparticles (CUR/NKSN, PTX/NKSN, CK/NKSN) were obained by the dialysis method, their physicochemical properties were determined and antitumor activity were evaluated. The NLS-KALA-SA nanoparticles were spherical shaped with an average size of 76.4 ± 7.6 mm and a zeta potential of 43.7 ± 5.8 mV. The drug-loaded NLS-KALA-SA nanoparticles were above 86.1% and 17.1% in entrapment efficiency and drug loading capacity, and had sustained drug release behavior. Biodistribution and cellular uptake study exhibited that PTX/NKSN mainly distributed in tumor site of A549-bearing mice, and coumarin-6(C6) loaded NLS-KALA-SA nanoparticle (C6/NKSN) was predominantly accumulated in the nucleus of A549 cells. Western blot analysis indicated that PTX/NKSN could more remarkably inhibit Bcl-2 expression and enhance the expression of Bax and Caspase-3 as compared to the controls in A549 cells. Cell apoptosis and antitumor activity study showed that PXT/NKSN could more obviously induce apoptosis of A549 cells compared with free PXT, the PTX/NKSN administration was more effective than free PTX for lung cancer treatment and displayed mild toxicity in A549-bearing mice. The results demonstrates that the NLS-KALA-SA nanoparticles system could enhance the antitumor effects of the encapsulated drug and reduce tissue toxicity due to its long circulating properties and tumor targeting, which might provide a promising strategy for lung cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
6. Dual-functional lipid polymeric hybrid pH-responsive nanoparticles decorated with cell penetrating peptide and folate for therapy against rheumatoid arthritis.
- Author
-
Zhao, Jinlong, Zhang, Xueyan, Sun, Xiangshi, Zhao, Menghui, Yu, Changhui, Lee, Robert J., Sun, Fengying, Zhou, Yulin, Li, Youxin, and Teng, Lesheng
- Subjects
- *
NANOPARTICLES , *SCANNING electron microscopes , *JUNO protein , *CRYSTALLIZATION , *KETOCONAZOLE - Abstract
Methotrexate (MTX), as a disease modifying antirheumatic drug (DMARD), was first line drug to treat rheumatoid arthritis. However, the severe side effect during long term and high dosage usage limit its application. The aim of this study was to develop dual-functional lipid polymeric hybrid pH-responsive nanoparticles to deliver MTX to inflamed joints selectively. The designed MTX loaded stearic acid-octa-arginine and folic acid decorated poly lactic-co-glycolic acid (PLGA) -PK3-based lipid polymeric hybrid nanoparticles (Sta-R8-FA-PPLPNs/MTX) were composed of PK3, Folate-PEG-PLGA, egg PC, and Sta-R8. The nanoparticles exhibited smooth spherical morphology and particle size of 100–150 nm. The in vitro release study indicated that MTX was released faster in phosphate buffered solution (PBS) of pH 5.0 than that in PBS of pH 7.4 from Sta-R8-FA-PPLPNs/MTX. The cellular uptake study revealed that Sta-R8-FA-PPLPNs/MTX were internalized through folate receptor mediated endocytosis into activated macrophages. Therapeutic effects on adjuvant-induced arthritis (AIA) rats further confirm that Sta-R8-FA-PPLPNs/MTX could be promising against rheumatoid arthritis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
7. Folate Receptor-Targeted Albumin Nanoparticles Based on Microfluidic Technology to Deliver Cabazitaxel.
- Author
-
Meng, Fanchao, Sun, Yating, Lee, Robert J., Wang, Guiyuan, Zheng, Xiaolong, Zhang, Huan, Fu, Yige, Yan, Guojun, Wang, Yifan, Deng, Weiye, Parks, Emily, Kim, Betty Y.S., Yang, Zhaogang, Jiang, Wen, and Teng, Lesheng
- Subjects
- *
ANIMAL experimentation , *CELL receptors , *COMPARATIVE studies , *DRUG delivery systems , *FOLIC acid , *NANOPARTICLES , *TUMORS , *ALBUMINS , *MICROFLUIDICS , *IN vitro studies , *CABAZITAXEL , *IN vivo studies , *PHARMACODYNAMICS - Abstract
Microfluidic technology (MF) has improved the formulation of nanoparticles (NPs) by achieving uniform particle size distribution, controllable particle size, and consistency. Moreover, because liquid mixing can be precisely controlled in the pores of the microfluidic chip, maintaining high mixing efficiency, MF exerts higher of NP encapsulation efficiency (EE) than conventional methods. MF-NPs-cabazitaxel (CTX) particles (MF-NPs-CTX) were first prepared by encapsulating CTX according to MF. Folate (FA)- Polyethylene glycol (PEG)-NPs-CTX particles (FA-PEG-NPs-CTX) were formulated by connecting FA to MF-NPs-CTX to endow NPs with targeted delivery capability. Accordingly, the mean particle size of FA-PEG-NPs-CTX increased by approximately 25 nm, as compared with MF-NPs-CTX. Upon morphological observation of FA-PEG-NPs-CTX and MF-NPs-CTX by transmission electron microscopy (TEM), all NPs were spherical and particle size distribution was uniform. Moreover, the increased delivery efficiency of CTX in vitro and its strong tumor inhibition in vivo indicated that FA-PEG-NPs-CTX had a powerful tumor-suppressive effect both in vitro and in vivo. In vivo imaging and pharmacokinetic data confirmed that FA-PEG-NPs-CTX had good drug delivery efficiency. Taken together, FA-PEG-NPs-CTX particles prepared using MF showed high efficient and targeted drug delivery and may have a considerable driving effect on the clinical application of targeting albumin NPs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
8. Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide.
- Author
-
Li, Hong, Liu, Yang, Chen, Lihua, Liu, Qibing, Qi, Shanshan, Cheng, Xinwei, Lee, Young B., Ahn, Chang-Ho, Kim, Deog Joong, and Lee, Robert J.
- Subjects
- *
NANOPARTICLES , *ANTINEOPLASTIC agents , *XENOGRAFTS , *CANCER treatment , *CANCER cells - Abstract
Background: RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.Purpose: To improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).Methods: F-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate-PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human carcinoma cellsin vitro and in a KB murine xenograft tumour modelin vivo for pharmacokinetics and antitumor activities.Results: The F-LAN-RX-0201 had a mean particle size of 108.6 ± 5.8 nm, zeta potential of 10.5 ± 3.2 mV and ASO loading efficiency of 71.5 ± 4.5%. In KB cells, uptake and Akt1 inhibition by F-LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with an IC50 of 11.9 μM. In contrast, LAN-RX-0201 showed lower cytotoxicity with an IC50 of 32.0 μM. No significant cytotoxicity was observed with up to 250 µM of free RX-0201. Pharmacokinetic studies showed that F-LAN-RX-0201 had a longer terminal half-life than free RX-0201 (442 vs. 219 min). In a KB xenograft tumour model, F-LAN-RX-0201 exhibited greater tumour inhibition than LAN-RX-0201 at 16 mg/kg. Moreover, F-LAN-RX-0201 at 16 mg/kg showed comparable tumour inhibition compared to free RX-0201 at a much higher dose of 90 mg/kg.Conclusions: F-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
9. Delivery of paclitaxel using nanoparticles composed of poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO).
- Author
-
Wang, Lijiang, Yao, Ju, Zhang, Xiaomin, Zhang, Yingxin, Xu, Chang, Lee, Robert J., Yu, Gary, Yu, Bo, and Teng, Lesheng
- Subjects
- *
NANOPARTICLES , *POLYETHYLENE oxide , *PACLITAXEL , *ZETA potential , *PHARMACOKINETICS , *DRUG delivery systems - Abstract
An amphiphilic block copolymer poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) was evaluated as a carrier for therapeutic delivery of paclitaxel (PTX). PEO-PBO and PTX form nanoparticles (NPs) by self-assembly upon hydration. The size of these NPs was about 92.71 nm and the zeta potential was −5.06 mV, which met the requirements for passive tumor targeting through the enhanced permeability and retention effect. Compared with a commonly used block copolymer poly(ethylene glycol)-b-poly-D,L-(lactic acid) (PEG-PDLLA), PEO-PBO forms nanoparticles with superior pharmacokinetic, biodistribution, and tumor inhibitory properties. Meanwhile, results of hemolysis study and CMC determination showed that PEO-PBO had better biocompatibility and stability than PEG-PDLLA. These data suggest that PEO-PBO has potential for application in drug delivery and warrant further evaluation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
10. Efficient delivery of the Bcl-2 antisense oligonucleotide G3139 via nucleus-targeted aCD33-NKSN nanoparticles.
- Author
-
Yan, Chengyun, Gu, Jiwei, Zhang, Yuan, Ma, Kailun, and Lee, Robert J.
- Subjects
- *
ACUTE myeloid leukemia , *OLIGONUCLEOTIDES , *GENE fusion , *NANOPARTICLES , *STEARIC acid , *CELL nuclei , *NANOMEDICINE - Abstract
[Display omitted] G3139 is an antisense oligodeoxyribonucleotide (ODN) developed as a Bcl-2 down-regulating agent for the treatment of acute myelogenous leukemia (AML). However, the clinical efficacy of G3139 has been shown to be limited due to its rapid plasma clearance and low permeability. To enhance the effective delivery of G3139, this work prepared a novel nano gene delivery vector (aCD33-NKSN) consisting of a CD33 antigbody (aCD33), a nuclear localization signal (NLS), gene fusion peptides (KALA), and stearic acid (SA) for CD33 antigen targeting and nuclear localization. The aCD33-NKSN/G3139 nanoparticles were spherical and uniformly sized with a positive charge and sustained release. They had an excellent G3139 loading capacity and colloidal stability. The aCD33-NKSN/G3139 delivered G3139 into the nucleus of Kasumi-1 cells and aCD33-NKSN/G3139 could more effectively inhibited Bcl-2 expression and induced apoptosis in Kasumi-1 cells versus free G3139. The aCD33-NKSN/G3139 administration was more effective at inhibiting tumor growth, and significantly prolonged the survival time of mice in contrast to free G3139. The results illustrate that aCD33-NKSN/G3139 nanoparticles could improve the antitumor activity of encapsulated G3139 due to aCD33 targeting and the ability to perform nuclear localization, The results offer a promising clinical application potential for the treatment of acute myeloid leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Efficient delivery of the Bcl-2 antisense oligonucleotide G3139 via nucleus-targeted aCD33-NKSN nanoparticles.
- Author
-
Yan, Chengyun, Gu, Jiwei, Zhang, Yuan, Ma, Kailun, and Lee, Robert J.
- Subjects
- *
ACUTE myeloid leukemia , *OLIGONUCLEOTIDES , *GENE fusion , *NANOPARTICLES , *STEARIC acid , *CELL nuclei , *NANOMEDICINE - Abstract
[Display omitted] G3139 is an antisense oligodeoxyribonucleotide (ODN) developed as a Bcl-2 down-regulating agent for the treatment of acute myelogenous leukemia (AML). However, the clinical efficacy of G3139 has been shown to be limited due to its rapid plasma clearance and low permeability. To enhance the effective delivery of G3139, this work prepared a novel nano gene delivery vector (aCD33-NKSN) consisting of a CD33 antigbody (aCD33), a nuclear localization signal (NLS), gene fusion peptides (KALA), and stearic acid (SA) for CD33 antigen targeting and nuclear localization. The aCD33-NKSN/G3139 nanoparticles were spherical and uniformly sized with a positive charge and sustained release. They had an excellent G3139 loading capacity and colloidal stability. The aCD33-NKSN/G3139 delivered G3139 into the nucleus of Kasumi-1 cells and aCD33-NKSN/G3139 could more effectively inhibited Bcl-2 expression and induced apoptosis in Kasumi-1 cells versus free G3139. The aCD33-NKSN/G3139 administration was more effective at inhibiting tumor growth, and significantly prolonged the survival time of mice in contrast to free G3139. The results illustrate that aCD33-NKSN/G3139 nanoparticles could improve the antitumor activity of encapsulated G3139 due to aCD33 targeting and the ability to perform nuclear localization, The results offer a promising clinical application potential for the treatment of acute myeloid leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Enhanced antitumor efficacy of vitamin E TPGS-emulsified PLGA nanoparticles for delivery of paclitaxel.
- Author
-
Sun, Yanbin, Yu, Bo, Wang, Guoying, Wu, Yongsheng, Zhang, Xiaomin, Chen, Yanmin, Tang, Suoqing, Yuan, Yuan, Lee, Robert J., Teng, Lesheng, and Xu, Shun
- Subjects
- *
ANTINEOPLASTIC agents , *POLYLACTIC acid , *NANOPARTICLES , *PACLITAXEL , *DRUG delivery systems , *PRECIPITATION (Chemistry) - Abstract
Nanoparticles are efficient delivery vehicles for cancer therapy such as paclitaxel (PTX). In this study, we formulated PTX into PLGA polymeric nanoparticles. Vitamin E TPGS was used as an emulsifier to stabilize the nanoparticle formulation. PTX was encapsulated in TPGS-emulsified polymeric nanoparticles (TENPs) by a nanoprecipitation method in ethanol–water system. The resultant PTX-TENPs showed a very uniform particle size (∼100 nm) and high drug encapsulation (>80%). The cytotoxicity of PTX-TENPs was examined in A549 lung cancer cell line. Preferential tumor accumulation of TENPs was observed in the A549 lung cancer xenograft model. Tumor growth was significantly inhibited by intravenous injection of PTX-TENPs. Our results suggested that the modified nanoprecipitation method holds great potential for the fabrication of the PTX loaded polymeric nanoparticles. TPGS can be used in the manufacture of polymeric nanoparticles for the controlled release of PTX and other anti-cancer drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
13. 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
14. Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia.
- Author
-
Yu, Bo, Mao, Yicheng, Bai, Li-Yuan, Herman, Sarah E. M., Wang, Xinmei, Ramanunni, Asha, Jin, Yan, Mo, Xiaokui, Cheney, Carolyn, Chan, Kenneth K., Jarjoura, David, Marcucci, Guido, Lee, Robert J., Byrd, John C., James Lee, L., and Muthusamy, Natarajan
- Subjects
- *
OLIGONUCLEOTIDES , *LIPOSOMES , *NANOPARTICLES , *B cells , *FLUDARABINE - Abstract
Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs), small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an integral part of their design. The limited success with free antisense ONs in hematologic malignancies in recent clinical trials has been attributed to the CpG motif-mediated, TLR-induced prosurvival effects and inefficient target modulation in desired cells. In an attempt to diminish their off-target prosurvival and proinflammatory effects and specific delivery, as a proof of principle, in the present study, we developed an Ab-targeted liposomal delivery strategy using a clinically relevant CD20 Ab (rituximab)-conjugated lipopolyplex nanoparticle (RIT-INP)- and Bcl-2-targeted antisense G3139 as archetypical antisense therapeutics. The adverse immunostimulatory responses were abrogated by selective B cell-targeted delivery and early endosomal compartmentalization of G3139-encapsulated RIT-INPs, resulting in reduced NF-κB activation, robust Bcl-2 down-regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity. Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP-G3139 administration in a disseminated xenograft leukemia model. The results of the present study demonstrate that CD20-targeted delivery overcomes the immunostimulatory properties of CpG-containing ON therapeutics and improves efficient gene silencing and in vivo therapeutic efficacy for B-cell malignancies. The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
15. Targeted nanoparticles enhanced flow electroporation of antisense oligonucleotides in leukemia cells
- Author
-
Wang, Shengnian, Zhang, Xulang, Yu, Bo, Lee, Robert J., and Lee, L. James
- Subjects
- *
ELECTROPORATION , *OLIGONUCLEOTIDES , *CHRONIC myeloid leukemia , *NANOPARTICLES , *MICROFLUIDICS , *GENE targeting , *TRANSFERRIN - Abstract
Abstract: Liposome nanoparticles (LNs) with a targeting ligand were used in a semi-continuous flow electroporation (SFE) device to enhance in vitro delivery of exogenous oligonucleotides (ODN). Nanoparticles comprising transferrin-targeted lipoplex encapsulating ODN G3139 were mixed with K562 cells (a chronic myeloid leukemia cell line) and incubated for half an hour to accomplish nanoparticle binding. The mixture was then flowed through a SFE channel where electric pulses were given. Better ODN delivery efficiency was achieved with an increase of ∼24% to the case in combination of non-targeted LNs and SFE, and ∼60% to the case using targeted LNs alone, respectively. The MTS assay results confirmed cell viability greater than 75%. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
16. Lipid-coated nano-calcium-phosphate (LNCP) for gene delivery
- Author
-
Zhou, Chenguang, Yu, Bo, Yang, Xiaojuan, Huo, Tianyao, Lee, L. James, Barth, Rolf F., and Lee, Robert J.
- Subjects
- *
CALCIUM phosphate , *GENE therapy , *NANOPARTICLES , *PLASMIDS , *GENE transfection , *LIPOSOMES , *GENETIC transformation - Abstract
Abstract: While calcium-phosphate has been used to deliver plasmid DNA (pDNA) for decades, the method is typically characterized by low and irreproducible transfection efficiency relative to the other non-viral approaches, such as liposomes and polymers. Here we report a novel gene transfer vector comprising lipid-coated nano-calcium-phosphate (LNCP) that provides consistently efficient and satisfactory pDNA delivery. It is based on core-shell nanoparticles comprising a calcium-phosphate core and a cationic lipid shell. This method, in contrast to the solution precipitation methods used in the past, yields colloidally stable calcium-phosphate nanoparticles inside the cationic liposomes. Our results indicate that the particle size and the size distribution of the LNCP remain virtually unchanged even after 21 days of storage. Atomic force microscopy measurements reveal that the LNCP have a 5-fold higher rigidity than common cationic liposomes. The LNCP transfected pDNA 24 times greater than the naked pDNA and 10-fold greater relative to the standard calcium-phosphate precipitation preparations, suggesting that the LNCP may have potential as a novel transfection agent for gene therapy. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
17. Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7α-APTADD to breast cancer cells
- Author
-
Zheng, Yu, Yu, Bo, Weecharangsan, Wanlop, Piao, Longzhu, Darby, Michael, Mao, Yicheng, Koynova, Rumiana, Yang, Xiaojuan, Li, Hong, Xu, Songlin, Lee, L. James, Sugimoto, Yasuro, Brueggemeier, Robert W., and Lee, Robert J.
- Subjects
- *
NANOPARTICLES , *COPOLYMERS , *TRANSFERRIN , *AROMATASE , *ENZYME inhibitors , *TARGETED drug delivery , *BIOCONJUGATES , *LIPIDS - Abstract
Abstract: Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7α-(4′-amino)phenylthio-1,4-androstadiene-3,17-dione (7α-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3±3.4%, mean diameter of 170.3±7.6nm and zeta potential of −18.9±1.5mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC50 value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and IC50 value of the nanoparticles was ranging from 1.90 to 3.41nM (n =3). The former is significantly lower than the latter (p <0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
18. 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
19. Cationic lipid-coated magnetic nanoparticles associated with transferrin for gene delivery
- Author
-
Pan, Xiaogang, Guan, Jingjiao, Yoo, Jung-Woo, Epstein, Arthur J., Lee, L. James, and Lee, Robert J.
- Subjects
- *
TRANSFERRIN , *BLOOD proteins , *CARRIER proteins , *NANOPARTICLES - Abstract
Abstract: Cationic lipid-coated magnetic nanoparticles (MPs) associated with transferrin were evaluated as gene transfer vectors in the presence of a static magnetic field. MPs were prepared by chemical precipitation and were surface-coated with cationic lipids, composed of DDAB/soy PC (60:40mole/mole). These cationic MPs were then combined with polyethylenimine (PEI) condensed plasmid DNA, followed by transferrin. The resulting magnetic electrostatic complexes retained relatively compact particle size and showed complete DNA condensation. Their transfection activity in the presence of a static magnetic field was evaluated by luciferase and green fluorescent protein (GFP) reporter genes. The magnetic complexes exhibited up to 300-fold higher transfection activity compared to commonly used cationic liposomes or cationic polymer complexes, based on luciferase assay. The enhancement in transfection activity was maximized when the cells were exposed to the vectors for a relatively short period of time (15min), or were treated in media containing 10% serum. Incorporation of transferrin further improved transfection efficiency of the cationic MPs. However, when cells were incubated for 4h in serum-free media, magnetic and non-magnetic vectors showed similar transfection efficiencies. In conclusion, transferrin-associated cationic MPs are excellent gene transfer vectors that can mediate very rapid and efficient gene transfer in vitro in the presence of a magnetic field. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
20. PLGA/PCADK composite microspheres containing hyaluronic acid–chitosan siRNA nanoparticles: A rational design for rheumatoid arthritis therapy.
- Author
-
Zhao, Menghui, Zhu, Tianyu, Chen, Jicong, Cui, Yaxin, Zhang, Xueyan, Lee, Robert J., Sun, Fengying, Li, Youxin, and Teng, Lesheng
- Subjects
- *
HYALURONIC acid , *RHEUMATOID arthritis , *SMALL interfering RNA , *MICROSPHERES , *ADJUVANT arthritis , *NANOPARTICLES - Abstract
Myeloid cell leukemia-1 (Mcl-1), a member of the Bcl-2 anti-apoptotic family, is overexpressed in the synovial macrophages of patients with rheumatoid arthritis (RA). Small interfering RNA (siRNA) Mcl-1 can induce macrophage apoptosis in the joints and is a potential therapeutic target of RA. Nevertheless, the application of siRNA is limited owing to its instability and susceptibility to degradation in vivo. To address these shortcomings, we developed composite microspheres (MPs) loaded with hyaluronic acid (HA)–chitosan (CS) nanoparticles (NPs). First, we synthesized HA–CS/siRNA NPs (HCNPs) using ionotropic gelation process. Then, HCNPs, as an internal aqueous phase, were loaded into poly (D, L-lactide-co-glycolide) (PLGA) and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) MPs using the double emulsion method. The NPs-in-MPs (NiMPs) composite system provided sustained release of NPs, protected siRNA against nuclease degradation in the serum, and could readily cross the cellular membrane. In addition, we evaluated the advantages of NiMPs in an adjuvant-induced arthritis rat model. Our experimental results demonstrate that NiMPs have greater pharmacodynamic effects than common MPs. Meanwhile, compared with HCNPs, NiMPs reduced the frequency of drug administration. Therefore, NiMPs are a promising and novel siRNA delivery vehicle for RA therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
21. Selenium-doped calcium carbonate nanoparticles loaded with cisplatin enhance efficiency and reduce side effects.
- Author
-
Zhao, Pengxuan, Li, Minsi, Chen, Yan, He, Chuanchuan, Zhang, Xiaojuan, Fan, Ting, Yang, Tan, Lu, Yao, Lee, Robert J., Ma, Xiang, Luo, Jun, and Xiang, Guangya
- Subjects
- *
DRUG side effects , *CALCIUM carbonate , *MICROEMULSIONS , *CARCINOGENS , *BONE cancer , *NANOPARTICLES , *CISPLATIN , *OSTEOSARCOMA - Abstract
Osteosarcoma is the bone tumor that most commonly affects children and teenagers with low survival rate because of metastatic relapse or recurrence. Cisplatin is a first-line chemotherapy for osteosarcoma. However, severe side effects limit its use in clinic. Selenium (Se) is an anticarcinogen that can protect normal tissues from side effects of chemotherapy. In this study, nanoparticles were used to co-deliver cisplatin and Se in a synergistic combination. Se-doped and lipid-coated calcium carbonate nanoparticles loaded with cisplatin (Pt/Se@CaCO 3 NPs) were prepared by a reverse microemulsion method. The NPs delivered cisplatin and Se to tumour cells at an optimal synergistic ratio of 1:1 (mol/mol) both in vitro and in an osteosarcoma xenograft model. These results demonstrate that Pt/Se@CaCO 3 NPs have great prospects for the osteosarcoma therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
22. Trastuzumab-Coated Nanoparticles Loaded With Docetaxel for Breast Cancer Therapy.
- Author
-
Zhang, Xueyan, Liu, Jiaxin, Li, Xiangyu, Li, Fang, Lee, Robert J., Sun, Fengying, Li, Youxin, Liu, Zongyu, and Teng, Lesheng
- Subjects
- *
POLYMERS , *BREAST cancer , *DOCETAXEL , *CANCER treatment , *NANOPARTICLES - Abstract
Docetaxel (DTX) is commonly used for breast cancer treatment. Tween 80 used for DTX dissolution in its clinical formulation causes severe hypersensitivity and other adverse reactions. In this study, trastuzumab (Tmab)-coated lipid-polymer hybrid nanoparticles (PLNs) were prepared, composed of poly (d, l -lactide- co -glycolide), PLGA; polyethylenimine (PEI); and lipids. The PLGA/PEI/lipid formed a hydrophobic core, while Tmab was electrostatically adsorbed on the surface of the PLNs as a ligand that targets human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. The resulting PLNs, electrostatically adsorbed Tmab-bearing PLGA/PEI/lipid nanoparticles (eTmab-PPLNs), had a mean particle size of 217.4 ± 13.36 nm, a ζ potential of 0.056 ± 0.315 mV, and good stability. In vitro, the eTmab-PPLNs showed increased cytotoxicity in HER2-postive BT474 cells but not in HER2-negative MCF7 cells. Studies of the ability of eTmab-PPLNs to target HER2 were performed. The uptake of eTmab-PPLNs was shown to be dependent on HER2 expression level. Therefore, eTmab-PPLNs provide a promising therapeutic for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
23. Thiophene Derivatives as Anticancer Agents and Their Delivery to Tumor Cells Using Albumin Nanoparticles.
- Author
-
Cai, Guangsheng, Wang, Simiao, Zhao, Lang, Sun, Yating, Yang, Dongsheng, Lee, Robert J., Zhao, Menghui, Zhang, Huan, and Zhou, Yulin
- Subjects
- *
THIOPHENE derivatives , *CELL-mediated cytotoxicity , *ANTINEOPLASTIC agents , *CELL growth , *DRUG delivery devices , *NANOPARTICLES , *ENCAPSULATION (Catalysis) - Abstract
A series of thiophene derivatives (TPs) were synthesized and evaluated for cytotoxicity in HepG2 and SMMC-7721 cell lines by MTT assay. TP 5 was identified as a potential anticancer agent based on its ability to inhibit tumor cell growth. Drawbacks of TPs, including poor solubility and high toxicity, were overcome through delivery using self-assembling HSA nanoparticles (NPs). The optimum conditions for TP 5-NPs synthesis obtained by adjusting the temperature and concentration of TP 5. The NPs had an encapsulation efficiency of 99.59% and drug-loading capacity of 3.70%. TP 5 was slowly released from TP 5-NPs in vitro over 120 h. HepG2 and SMMC-7721 cell lines were employed to study cytotoxicity of TP 5-NPs, which exhibited high potency. ROS levels were elevated and mitochondrial membrane potentials reversed when the two cell lines were treated with TP 5-NPs for 12 h. Cellular uptake of fluorescence-labeled TP 5-NPs in vitro was analyzed by flow cytometry and laser confocal scanning microscopy. Fluorescence intensity increased over time, suggesting that TP 5-NPs were efficiently taken up by tumor cells. In conclusion, TP 5-NPs showed great promise as an anticancer therapeutic agent. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.