17 results on '"Jiang, Chen"'
Search Results
2. Targeting Caspase-3 as Dual Therapeutic Benefits by RNAi Facilitating Brain-Targeted Nanoparticles in a Rat Model of Parkinson’s Disease
- Author
-
Liu, Yang, Guo, Yubo, An, Sai, Kuang, Yuyang, He, Xi, Ma, Haojun, Li, Jianfeng, Lv, Jing, Zhang, Ning, and Jiang, Chen
- Subjects
CASPASE inhibitors ,RNA interference ,NANOMEDICINE ,PARKINSON'S disease ,APOPTOSIS ,INFLAMMATION ,LABORATORY rats - Abstract
The activation of caspase-3 is an important hallmark in Parkinson’s disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson’s disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson’s disease rats’ brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
3. Fas ligand gene transfer effectively induces apoptosis in head and neck cancer cells.
- Author
-
Ji, Xiaojun, Jiang, Chen, Liu, Yuhe, Bu, Dingfang, and Xiao, Shuifang
- Subjects
- *
CANCER cells , *APOPTOSIS , *BIOLOGICAL assay , *BIOPHYSICS , *EPITHELIAL cells , *FLOW cytometry , *GENE therapy , *GENETIC techniques , *RESEARCH methodology , *POLYMERASE chain reaction , *RESEARCH funding , *REVERSE transcriptase polymerase chain reaction , *CERAMIDASES , *CANCER treatment - Abstract
Conclusion: Fas ligand (FasL) gene therapy may provide a new efficient therapeutic model for head and neck squamous cell cancer (HNSCC). Acid ceramidase (AC) may not play an important role in the sensitivity of HNSCC cell lines to Fas-induced apoptosis. Objectives: The aims of this study were to investigate the efficacy of FasL gene therapy for HNSCC in vitro and to determine whether the expression of AC in different kinds of HNSCC cell lines is related to the sensitivity of HNSCC cell lines to Fas-mediated apoptotic induction. Methods: Three HNSCC cell lines (Hep-2, MMSI, and SCCVII) were transfected with pEGFP-FasL, a plasmid containing a modified human FasL gene fused to enhanced green fluorescent protein (GFP). pEGFP-C1, a plasmid containing the GFP gene alone, was used as a control. Cell death was observed by fluorescence imaging and quantified using a tetrazolium-based (MTS) assay. SCCVII cells were analyzed by flow cytometry to determine the presence of apoptotic induction. Hep-2 and MMSI cells were evaluated by quantitative real-time PCR to evaluate the expression of AC. Results: Transfection of pEGFP-FasL plasmid was shown to be able to induce cell death, the sensitivity of Fas-mediated apoptosis in HNSCC was different, and the level of AC did not correlate with the sensitivity of HNSCC cells to Fas-induced apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
4. Differentiation of Mouse Induced Pluripotent Stem Cells into a Multipotent Keratinocyte Lineage.
- Author
-
Bilousova, Ganna, Jiang Chen, and Roop, Dennis R.
- Subjects
- *
STEM cells , *CELL differentiation , *KERATINOCYTES , *EMBRYONIC stem cells , *SKIN diseases , *GENE therapy - Abstract
Recent breakthroughs in the generation of induced pluripotent stem cells (iPSCs) have provided a novel renewable source of cells with embryonic stem cell-like properties, which may potentially be used for gene therapy and tissue engineering. Although iPSCs have been differentiated into various cell types, iPSC-derived keratinocytes have not yet been obtained. In this study, we report the in vitro differentiation of mouse iPSCs into a keratinocyte lineage through sequential applications of retinoic acid and bone-morphogenetic protein-4 and growth on collagen IV-coated plates. We show that iPSCs can be differentiated into functional keratinocytes capable of regenerating a fully differentiated epidermis, hair follicles, and sebaceous glands in an in vivo environment. Keratinocytes derived from iPSCs displayed characteristics similar to those of primary keratinocytes with respect to gene and protein expression, as well as their ability to differentiate in vitro and to reconstitute normal skin and its appendages in an in vivo assay. At present, no effective therapeutic treatments are available for many genetic skin diseases. The development of methods for the efficient differentiation of iPSCs into a keratinocyte lineage will enable us to determine whether genetically corrected autologous iPSCs can be used to generate a permanent corrective therapy for these diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
5. Mouse Models in Preclinical Studies for Pachyonychia Congenita.
- Author
-
Jiang Chen and Roop, Dennis R.
- Subjects
- *
GENOMES , *GENETIC disorders , *GENETICS , *SKIN diseases , *DERMATOLOGY - Abstract
The similarities between the human and mouse genomes often allow researchers to make accurate predictions about the roles of their human counterparts. Because of the similar physiology between these two mammals, mice are used extensively in the laboratory to investigate the mechanisms of human diseases. Furthermore, mice provide us with the option of testing the toxicity of drugs and the safety of therapeutic approaches prior to human application. Here, we review the existing mouse models involving the keratin genes (K6a, K6b, K16, and K17) that cause the human genetic disorder pachyonychia congenita (PC). We also suggest methods to more accurately model this autosomal dominant skin condition in the mouse in order to better understand the pathophysiological processes underlying PC and importantly, provide a test-bed for testing emerging therapies in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
6. Transluminal Gene Transfer into Brain Capillary Endothelial Cells In Vivo with HVJ-liposomes.
- Author
-
Jiang, Chen, Matsuo, Hirotami, Koyabu, Noriko, Ohtani, Hisakazu, Fujimoto, Hidenori, Yonemitsu, Yoshikazu, Kaneda, Yasufumi, Naito, Mikihiko, Tsuruo, Takashi, and Sawada, Yasufumi
- Subjects
- *
GENETIC transformation , *GENE therapy , *ENDOTHELIUM , *THERAPEUTICS , *GENETIC engineering - Abstract
Bioactive proteins or peptides cannot be effectively delivered into brain capillary endothelial cells (BCECs) or brain parenchyma. In this study, we selectively transferred Escherichia coli β-galactosidase gene (β-gal) as a model gene into BCECs by using the hemagglutination virus of Japan (HVJ)-liposomes. HVJ-liposomes encapsulating a β-gal plasmid were used to transfect MBEC4 cells in vitro , and were administrated via the internal carotid artery to rat in vivo . Success of the procedure was confirmed by the detection of 116 kDa β-gal protein in transfected MBEC4 cells and in brain capillaries isolated from transfected rats, by Western blot analysis and histological staining. The enzymatic activities of β-galactosidase were 5- to 10-fold and 20-fold higher than when β-gal-containing liposomes without fusogenic activity (uncoated liposomes) or plasmid alone were employed in vitro and in vivo , respectively. Thus, HVJ-liposomes were demonstrated to be a useful vector to transfer a foreign gene into the brain capillary endothelium in vivo via the transluminal route. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
7. Brain-targeted co-delivery of therapeutic gene and peptide by multifunctional nanoparticles in Alzheimer's disease mice.
- Author
-
Liu, Yang, An, Sai, Li, Jianfeng, Kuang, Yuyang, He, Xi, Guo, Yubo, Ma, Haojun, Zhang, Yu, Ji, Bin, and Jiang, Chen
- Subjects
- *
ALZHEIMER'S disease treatment , *NANOPARTICLES , *GENE delivery techniques , *NANOCARRIERS , *BRAIN physiology , *LABORATORY mice - Abstract
Multifunctional nanocarriers are increasingly promising for disease treatment aimed to regulate multiple pathological dysfunctions and overcome barriers in drug delivery. Here we develop a multifunctional nanocarrier for Alzheimer's disease (AD) treatment by achieving therapeutic gene and peptide co-delivery to brain based on PEGylated dendrigraft poly- l -lysines (DGLs) via systemic administration. The dendritic amine-rich structure of DGLs provides plenty reaction sites and positive charge for drug loading. Successful co-delivery of drugs overcoming the blood–brain barrier by brain-targeted ligand modification was demonstrated both in vitro and in vivo . The pharmacodynamics study of the system following multiple-dosing treatment was verified in transgenic AD mice. Down-regulation of the key enzyme in amyloid-β formation was achieved by delivering non-coding RNA plasmid. Simultaneous delivery of the therapeutic peptide into brain leads to reduction of neurofibrillary tangles. Meanwhile, memory loss rescue in AD mice was also observed. Taken together, the multifunctional nanocarrier provides an excellent drug co-delivery platform for brain diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
8. Choline transporter-targeting and co-delivery system for glioma therapy.
- Author
-
Li, Jianfeng, Guo, Yubo, Kuang, Yuyang, An, Sai, Ma, Haojun, and Jiang, Chen
- Subjects
- *
CHOLINE , *GLIOMA treatment , *DRUG delivery systems , *CANCER treatment , *GENE therapy , *CANCER chemotherapy , *TUMOR necrosis factors , *BLOOD-brain barrier - Abstract
Abstract: Combination of gene therapy and chemotherapy is a promising approach for glioma therapy. In this study, a co-delivery system of plasmid encoding human tumor necrosis factor-related apoptosis-inducing ligand (pORF-hTRAIL, Trail) and doxorubicin (DOX) has been simply constructed in two steps. Firstly, DOX was intercalated into Trail to form a stable complex. Secondly, DOX-Trail complex was condensed by Dendrigraft poly-l-lysine (DGL) to form a nanoscaled co-delivery system. Choline transporters are both expressed on blood–brain barrier (BBB) and glioma, Herein, a choline derivate with high choline transporter affinity was chosen as BBB and glioma dual targeting ligand. Choline-derivate modified co-delivery system showed higher cellular uptake efficiency and cytotoxicity than unmodified co-delivery system in U87 MG cells. In comparison with single medication or unmodified delivery system, Choline-derivate modified co-delivery system induced more apoptosis both in vitro and in vivo. The therapeutic efficacy on U87 MG bearing xenografts further confirmed the predominance of this dual targeting and co-delivery system. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
9. T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma dual targeting.
- Author
-
Kuang, Yuyang, An, Sai, Guo, Yubo, Huang, Shixian, Shao, Kun, Liu, Yang, Li, Jianfeng, Ma, Haojun, and Jiang, Chen
- Subjects
- *
PEPTIDES , *NANOMEDICINE , *RNA interference , *GLIOMA treatment , *TARGETED drug delivery , *CANCER treatment , *GENE therapy , *DRUG delivery systems , *THERAPEUTICS - Abstract
Abstract: Among all the malignant brain tumors, glioma is the deadliest and most common form with poor prognosis. Gene therapy is regarded as a promising way to halt the progress of the disease or even cure the tumor and RNA interference (RNAi) stands out. However, the existence of the blood–brain barrier (BBB) and blood tumor barrier (BTB) limits the delivery of these therapeutic genes. In this work, the delivery system targeting to the transferrin (Tf) receptor highly expressed on both BBB and glioma was successfully synthesized and would not compete with endogenous Tf. U87 cells stably express luciferase were employed here to simulate tumor and the RNAi experiments in vitro and in vivo validated that the gene silencing activity was 2.17-fold higher with the targeting ligand modification. The dual-targeting gene delivery system exhibits a series of advantages, such as high efficiency, low toxicity, stability and high transaction efficiency, which may provide new opportunities in RNAi therapeutics and nanomedicine of brain tumors. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
10. Tumor targeting and microenvironment-responsive nanoparticles for gene delivery.
- Author
-
Huang, Shixian, Shao, Kun, Kuang, Yuyang, Liu, Yang, Li, Jianfeng, An, Sai, Guo, Yubo, Ma, Haojun, He, Xi, and Jiang, Chen
- Subjects
- *
TUMOR treatment , *TARGETED drug delivery , *NANOMEDICINE , *CANCER treatment , *GENE therapy , *DRUG delivery systems , *MATRIX metalloproteinases , *GENETIC regulation - Abstract
Abstract: A tumor targeting nanoparticle system has been successfully developed to response to the lowered tumor extracellular pH (pHe) and upregulated matrix metalloproteinase 2 (MMP2) in the tumor microenvironment. The nanoparticles are modified with activatable cell-penetrating peptide (designated as dtACPP) that's dual-triggered by the lowered pHe and MMP2. In dtACPP, the internalization function of cell-penetrating peptide (CPP) is quenched by a pH-sensitive masking peptide, linking by a MMP2 substrate. The masking peptide is negatively charged to quench the cationic CPP well after systemic administration. Hence, dtACPP-modified nanoparticles possesses passive tumor targetability via the enhanced permeability and retention (EPR) effect. Once reaching the tumor microenvironment, the pre-existing attraction would be eliminated due to the lowered pHe, accompanying the linker cleaved by MMP2, dtACPP would be activated to expose CPP to drive the nanoparticles' internalization into the intratumoral cells. The studies of plasmid DNA loading, toxicity assessment, cellular uptake, tumor targeting delivery, and gene transfection demonstrate that dtACPP-modified nanoparticle system is a potential candidate for tumor targeting gene delivery. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
11. Gene and doxorubicin co-delivery system for targeting therapy of glioma
- Author
-
Liu, Shuhuan, Guo, Yubo, Huang, Rongqin, Li, Jianfeng, Huang, Shixian, Kuang, Yuyang, Han, Liang, and Jiang, Chen
- Subjects
- *
GLIOMA treatment , *DOXORUBICIN , *DRUG delivery systems , *TARGETED drug delivery , *GENE therapy , *CANCER chemotherapy , *DRUG design - Abstract
Abstract: The combination of gene therapy and chemotherapy is a promising treatment strategy for brain gliomas. In this paper, we designed a co-delivery system (DGDPT/pORF-hTRAIL) loading chemotherapeutic drug doxorubicin and gene agent pORF-hTRAIL, and with functions of pH-trigger and cancer targeting. Peptide HAIYPRH (T7), a transferrin receptor-specific peptide, was chosen as the ligand to target the co-delivery system to the tumor cells expressing transferrin receptors. T7-modified co-delivery system showed higher efficiency in cellular uptake and gene expression than unmodified co-delivery system in U87 MG cells, and accumulated in tumor more efficiently in vivo. DOX was covalently conjugated to carrier though pH-trigged hydrazone bond. In vitro incubation of the conjugates in buffers led to a fast DOX release at pH 5.0 (intracellular environment) while at pH 7.4 (blood) the conjugates are relatively stable. The combination treatment resulted in a synergistic growth inhibition (combination index, CI < 1) in U87 MG cells. The synergism effect of DGDPT/pORF-hTRAIL was verified in vitro and in vivo. In vivo anti-glioma efficacy study confirmed that DGDPT/pORF-hTRAIL displayed anti-glioma activity but was less toxic. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
12. Dual targeting effect of Angiopep-2-modified, DNA-loaded nanoparticles for glioma
- Author
-
Huang, Shixian, Li, Jianfeng, Han, Liang, Liu, Shuhuan, Ma, Haojun, Huang, Rongqin, and Jiang, Chen
- Subjects
- *
PEPTIDE drugs , *DNA , *NANOPARTICLES , *GLIOMAS , *TARGETED drug delivery , *APOPTOSIS , *LIGANDS (Biochemistry) , *TUMOR necrosis factors , *GENE therapy - Abstract
Abstract: Gene therapy offers a promising cure of brain glioma and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce cell apoptosis of glioma selectively without affecting the normal cells. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the principal vector. Angiopep-2, which can target to the low-density lipoprotein receptor-related protein-1 (LRP1) expressed on BCECs and glial cells, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG) and then complexed with the DNA, designated as PAMAM-PEG-Angiopep/DNA nanoparticles (NPs). The cellular uptake mechanism explored in glial cells showed that the DNA of PAMAM-PEG-Angiopep/DNA NPs entered into the nuclei through the endosome/lysosome pathway. The in vivo biodistribution of PAMAM-PEG-Angiopep/DNA NPs in the brain especially the tumor site was higher than that of PAMAM-PEG/DNA NPs and PAMAM/DNA NPs. Furthermore, the TUNEL analysis showed a more wide-extended apoptosis in the PAMAM-PEG-Angiopep/pORF-TRAIL NPs treated group, compared to other groups including commercial Temozolomide-treated one. The median survival time of PAMAM-PEG-Angiopep/pORF-TRAIL NPs and Temozolomide treated on brain tumor-bearing mice was 61 and 49 days respectively, significantly longer than that of other groups. Besides, the NPs suggested low cytotoxicity after in vitro transfection. Thus, the results showed that Angiopep-2 could be exploited as a specific ligand to cross the BBB and targeted to glial cells, and PAMAM-PEG-Angiopep/DNA NPs can be a potential non-viral delivery system for gene therapy of glial tumor. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
13. Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via intravenous administration
- Author
-
Huang, Rongqin, Ke, Weilun, Han, Liang, Li, Jianfeng, Liu, Shuhuan, and Jiang, Chen
- Subjects
- *
SCORPION venom , *NANOPARTICLES , *INTRAVENOUS therapy , *DRUG administration , *GLIOMA treatment , *CANCER treatment , *GENE therapy , *LIGANDS (Biochemistry) , *POLYAMINES - Abstract
Abstract: Gene therapy offers great potential for brain glioma. However, therapeutic genes could not reach glioma spontaneously. A glioma-targeting gene delivery system is highly desired to transfer exogenous genes throughout the tumor focus. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the main vector. Chlorotoxin (CTX), which has been demonstrated to bind specifically to receptor expressed in glioma, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM–PEG–CTX. The cellular uptake of CTX itself was observed apparently in C6 glioma cells, almost not in 293 cells. The modification of CTX could significantly increase the cellular uptake of vectors and the DNA-loaded nanoparticles (NPs) in C6 cells. The in vivo distribution of PAMAM–PEG–CTX/DNA NPs in the brain was higher than that of PAMAM/DNA NPs and PAMAM–PEG/DNA NPs. Furthermore, the gene expression of PAMAM–PEG–CTX/DNA NPs was higher and broader in glioma than that of unmodified and PEG-modified counterparts. The TUNEL analysis showed a more wide-extended apoptosis in the CTX-modified group, compared to other groups including commercial temozolomide group. The median survival time of CTX-modified group and temozolomide group was 59.5 and 49 days, respectively, significantly longer than that of other groups. The results suggested that CTX could be exploited as a special glioma-targeting ligand, and PAMAM–PEG–CTX/DNA NPs is a potential non-viral delivery system for gene therapy of glioma via intravenous administration. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
14. Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model
- Author
-
Huang, Rongqin, Ke, Weilun, Liu, Yang, Wu, Dongdong, Feng, Linyin, Jiang, Chen, and Pei, Yuanying
- Subjects
- *
PARKINSON'S disease treatment , *GENE therapy , *LACTOFERRIN , *NANOPARTICLES , *ROTENONE , *BRAIN diseases , *BLOOD-brain barrier , *PARKINSON'S disease , *ANIMAL models in research , *DISEASE risk factors - Abstract
Abstract: Background: Gene therapy is considered one of the most promising approaches to develop an effective treatment for Parkinson''s disease (PD). The existence of blood-brain barrier (BBB) significantly limits its development. In this study, lactoferrin (Lf)-modified nanoparticles (NPs) were used as a potential non-viral gene vector due to its brain-targeting and BBB-crossing ability. Methods and results: The neuroprotective effects were examined in a rotenone-induced chronic rat model of PD after treatment with NPs encapsulating human glial cell line-derived neurotrophic factor gene (hGDNF) via a regimen of multiple dosing intravenous administration. The results showed that multiple injections of Lf-modified NPs obtained higher GDNF expression and this gene expression was maintained for a longer time than the one with a single injection. Multiple dosing intravenous administration of Lf-modified NPs could significantly improve locomotor activity, reduce dopaminergic neuronal loss, and enhance monoamine neurotransmitter levels on rotenone-induced PD rats, which indicates its powerful neuroprotective effects. Conclusion: The findings may have implications for long-term non-invasive gene therapy for neurodegenerative diseases in general. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
15. Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer
- Author
-
Ke, Weilun, Shao, Kun, Huang, Rongqin, Han, Liang, Liu, Yang, Li, Jianfeng, Kuang, Yuyang, Ye, Liya, Lou, Jinning, and Jiang, Chen
- Subjects
- *
GENE therapy , *TARGETED drug delivery , *DENDRIMERS in medicine , *LIGANDS (Biochemistry) , *BRAIN , *NANOPARTICLES , *POLYETHYLENE glycol , *LOW density lipoproteins - Abstract
Abstract: Angiopep targeting to the low-density lipoprotein receptor-related protein-1 (LRP1) was identified to exhibit high transcytosis capacity and parenchymal accumulation. In this study, it was exploited as a ligand for effective brain-targeting gene delivery. Polyamidoamine dendrimers (PAMAM) were modified with angiopep through bifunctional PEG, then complexed with DNA, yielding PAMAM–PEG–Angiopep/DNA nanoparticles (NPs). The angiopep-modified NPs were observed to be internalized by brain capillary endothelial cells (BCECs) through a clathrin- and caveolae-mediated energy-depending endocytosis, also partly through marcopinocytosis. Also, the cellular uptake of the angiopep-modified NPs were competed by angiopep-2, receptor-associated protein (RAP) and lactoferrin, indicating that LRP1-mediated endocytosis may be the main mechanism of cellular internalization of angiopep-modified NPs. And the angiopep-modified NPs showed higher efficiency in crossing blood–brain barrier (BBB) than unmodified NPs in an in vitro BBB model, and accumulated in brain more in vivo. The angiopep-modified NPs also showed higher efficiency in gene expressing in brain than the unmodified NPs. In conclusion, PAMAM–PEG–Angiopep showed great potential to be applied in designing brain-targeting drug delivery system. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
16. Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles
- Author
-
Liu, Yang, Huang, Rongqin, Han, Liang, Ke, Weilun, Shao, Kun, Ye, Liya, Lou, Jinning, and Jiang, Chen
- Subjects
- *
GENE therapy , *BRAIN disease treatment , *VIRAL proteins , *RABIES virus , *GLYCOPROTEINS , *DENDRIMERS in medicine , *LIGANDS (Biochemistry) , *NANOPARTICLES , *GENETIC vectors - Abstract
Abstract: A 29 amino-acid peptide derived from the rabies virus glycoprotein (RVG29) was exploited as a ligand for efficient brain-targeting gene delivery. RVG29 was modified on polyamidoamine dendrimers (PAMAM) through bifunctional PEG, then complexed with DNA, yielding PAMAM–PEG–RVG29/DNA nanoparticles (NPs). The NPs were observed to be uptaken by brain capillary endothelial cells (BCECs) through a clathrin and caveolae mediated energy-depending endocytosis. The specific cellular uptake can be inhibited by free RVG29 and GABA but not by nicotinic acetylcholine receptor (nAchR) agonists/antagonists, indicating RVG29 probably relates to the GABAB receptor besides nAchR reported previously. PAMAM–PEG–RVG29/DNA NPs showed higher blood-brain barrier (BBB)-crossing efficiency than PAMAM/DNA NPs in an in vitro BBB model. In vivo imaging showed that the NPs were preferably accumulated in brain. The report gene expression of the PAMAM–PEG–RVG29/DNA NPs was observed in brain, and significantly higher than unmodified NPs. Thus, PAMAM–PEG–RVG29 provides a safe and noninvasive approach for the gene delivery across the BBB. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
17. The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain
- Author
-
Huang, Rongqin, Ke, Weilun, Liu, Yang, Jiang, Chen, and Pei, Yuanying
- Subjects
- *
THERAPEUTICS , *GENE therapy , *BLOOD proteins , *ANTITHROMBINS - Abstract
Abstract: Development of an efficient gene vector is a key-limiting factor of brain gene therapy. In this study, lactoferrin (Lf), for the first time, was investigated as a brain-targeting ligand in the design of polyamidoamine (PAMAM)-based non-viral gene vector to the brain. Using polyethyleneglycol (PEG) as a spacer, PAMAM–PEG–Lf was successfully synthesized. This vector showed a concentration-dependent manner in the uptake in brain capillary endothelial cells (BCECs). The brain uptake of PAMAM–PEG–Lf was 2.2-fold compared to that of PAMAM–PEG–transferrin (Tf) in vivo. The transfection efficiency of PAMAM–PEG–Lf/DNA complex was higher than that of PAMAM–PEG–Tf/DNA complex in vitro and in vivo. The results of frozen sections showed the widespread expression of an exogenous gene in mouse brain via intravenous administration. With a PAMAM/DNA weight ratio of 10:1, the brain gene expression of the PAMAM–PEG–Lf/DNA complex was about 2.3-fold when compared to that of the PAMAM–PEG–Tf/DNA complex. These results provide evidence that PAMAM–PEG–Lf can be exploited as a potential non-viral gene vector targeting to the brain via noninvasive administration. Lf is a promising ligand for the design of gene delivery systems targeting to the brain. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.