The lack of safe and efficient gene delivery systems is a major obstacle to achieve successful human gene *** synthetic gene delivery systems,although safer and more versatile than natural viruses,generally do not pos...
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The lack of safe and efficient gene delivery systems is a major obstacle to achieve successful human gene *** synthetic gene delivery systems,although safer and more versatile than natural viruses,generally do not possess the required delivery *** recent years,with the growing understanding the mechanisms of non-viral gene delivery,and inspired by the viral structures and functions,much effort has been directed to the development of intelligent polymers based bio-inspired and biomimetic multifunctional gene delivery *** polymers show promise in gene delivery due to their branched and layered architectures,globular shape and multivalent groups on their surface[1].Arginine functionalized L-lysine-based peptide dendrimers demonstrated efficient gene delivery[2,3].Furthermore,supramolecular self-assembly of peptide dendrimers based capsid-like nanostructure,they could also serve as pH-responsive nanovehicles and use to develop towards artificial virus for gene delivery[4,5].Low aggregated magnetic gene complexes have realized serum resistance and tumor accumulation effect for PEI-mediated gene transfection in vitro and in vivo,and the mechanism under this serum-tolerant transfection was defined[6].These structures contain elements that mimic the delivery functions and structures of viral particles and surface domains that shield against undesired biological interactions and enable tumor accumulatioa Recently,the dynamic ternary polyplexes based on disulfide bond modified hyaluronic acid and diselenMe conjugated ohgoethylenimine were designed for virus-mimicking gene delivery systems[7-9].With virus-like entry functions,the dynamic nanovehicles recognize the cues provided by cells and sense their biologic micro-environment,respond in a more dynamic manner to alterations in enzyme or redox environment both at tumor site and in the cell,undergo programmed molecular structural changes compatible with the different gene delivery steps to mod
Objective:In this research,a novel vinoreIbine-loaded aptamer（Apt） conjugated lipid-polymer hybrid nanoparticles（Apt-NP/VRL） were constructed for specific targeting MUC1 protein over expressed tumor ***:Apt-NP/VRL...
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Objective:In this research,a novel vinoreIbine-loaded aptamer（Apt） conjugated lipid-polymer hybrid nanoparticles（Apt-NP/VRL） were constructed for specific targeting MUC1 protein over expressed tumor ***:Apt-NP/VRL were prepared by self-assembling method using lecithin,DSPE-PEG2000-COOH,and poly（lactic-co-glycolic acid）(PLGA) as carrier *** formulation was optimized by orthogonal *** aptamer was conjugated to DSPE-PEG2000-COOH through EDC and NHS coupling（Figure 1）.Though changing the ratio of DSPE-PEG2ooo-Apt,NPs with different aptamer densities were synthesized and ***-6 labeled nanoparticles（Apt-NP/Cou-6） were prepared to evaluate the cellular uptake *** anti-tumor activity of Apt-NP/VRL to MCF-7 cell and HpG2 cell was ***:TEM indicated Apt-NP/VRL were about 128.1-166.5 nm,with a core-shell construction and the shell was 10 nm（Figure 2A）.XPS showed Apt was successfully conjugated to the surface of NP/VRL（Figure 2B）.The encapsulation efficiency was50.42-57.88%.The MCF-7 cell uptake of Apto.5-NP/VRL,Apti-NP/VRL,Apt-NP/VRL,Apt-NP/VRL,Apt-NP/VRL were increased with the increase of aptamer density（Figure 3）,and Figure 4 showed that the uptake of Apt-NP/VRL has been enhanced compared with Apto-NP/VRL in MCF-7 cells,indicating increased aptamer density improved targeting efficiency（p<0.05）.By increasing aptamer density,there was a increase in the inhibitory of MCF cell by Apto.5-NP/VRL,Apt-NP/VRL,Apt-NP/VRL,Apt-NP/VRL,Apt-NP/VRL compared with HepG2 cell（p<0.05）(Figure 5).All the results indicating that conjugate of aptamer has enhanced cellular uptake and toxicity of Apt-NP/VRL to MUC1 cell（p<0.05）.Conclusion:Aptamer conjugated lipid-polymer hybrid nanoparticles has been fabricated for MUC1 over expressed cancer cell targeting and ***-NP/VRL can delivery drugs specifically to MUC1 over expressed cancer cells which enhanced cell uptake and *** increasing the aptamer density on the su
Objective:There are very little available reports about the interaction of PLGA nanoparticle with cytochrome P450 *** aim of this study was to investigate the inhibitory effects of PLGA nanoparticles with different si...
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Objective:There are very little available reports about the interaction of PLGA nanoparticle with cytochrome P450 *** aim of this study was to investigate the inhibitory effects of PLGA nanoparticles with different sizes on rat hepatic cytochrome P450 enzymes(CYP1 A,CYP3 A,CYP2B,CYP2 D,CYP2C) ***:The inhibitory effects of PLGA nanoparticles(0.1,0.2,0.4,0.6,0.8,1.0mg/mL) on the major rat hepatic cytochrome P450 enzymes(CYP1A,CYP3 A,CYP2B,CYP2 D,CYP2C) activities were examined using rat liver ***(CYP3A),testosterone(CYP3A),phenacetin(CYP1A),tolbutamide(CYP2C),S-mephenytoin(CYP2C) and dextromethorphan(CYP2D) were selected as probe substrates,***:Five different sizes of PLGA NPs with mean particle sizes of around 60 nm(name as PLGA NPs-1),110 nm(name as PLGANPs-2),150 nm(name as PLGA NPs-3),300 nm(name as PLGA NPs-4) and 450 nm(name as PLGA NPs-5) were *** polydispersity indexs(PDI) were all less than 0.2,and the zeta potential was between-3 and-36 *** IC50 values for these five different sizes PLGANPs on CYP 2C,CYP2 D,CYP3 A(testosterone was used as probe substrates) were all more than 1 mg/mL indicating that PLGA NPs had no inhibitory effect on tolbutamide4-hydroxylase,(S)-mephenytoin 4-hydroxylase,dextromethorphan O-demethylase and testosterone 6β-*** CYP 1A and CYP3A(midazolam was chosed as probe substrates),only the IC50 values of PLGA NPs-4(IC50=0.6331 mg/mL for CYP3A) and PLGA NPs-5(IC50=0.8972 mg/mL for CYP1 A,IC50=0.9667 mg/mL for CYP3A) were less than 1 mg/mL,which indicated larger PLGA NPs had some influence but not small ones(PLGANPs-1,2,3).When the concentration of PLGANPs reached 1 mg/mL,the remain activities of CYP1A(not for PLGA NPs-4),CYP3 A,CYP2B,CYP2 D,CYP2C by PLGA NPs-4 and PLGA NPs-5 were significantly decreased compared with PLGANPs-1,PLGANPs-2,PLGA NPs-3,***:PLGA nanoparticles cannot inhibit the metabohsm of xenobiotics by the CYP450 system in rat
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