OBJECTIVE To investigate the effect of polyethylene imine glycol （PEI-PEG）/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of t...OBJECTIVE To investigate the effect of polyethylene imine glycol （PEI-PEG）/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. METHODS PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay （mononuclear cell direct cytotoxicity assay）, and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. RESULTS After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was （80.4 ± 5.6）% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to （59.7 ± 3.0）% after siRNA-CD44v6 was inhibited. CONCLUSION PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection e. ciency, less cytotoxicity and an easily alterable vector structure.展开更多
A novel kind of copolymer with ABA-type block structure was synthesized by anionic ring-opening polymerization of beta-butyrolactone (beta-BL) in the presence of a PEG-based dicarboxylates as macroinitiators which wer...A novel kind of copolymer with ABA-type block structure was synthesized by anionic ring-opening polymerization of beta-butyrolactone (beta-BL) in the presence of a PEG-based dicarboxylates as macroinitiators which were prepared by the esterification of aliphatic cyclic anhydride and poly(ethylene glycol) (PEG) oligomers (M-n = 2000, 4000 and 6000) and conversion of potassium dicarboxylates. The resultant copolymers as well as the intermediates were characterized by IR, H-1-NMR and GPC.展开更多
Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feas...Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.展开更多
Antibody targeted delivery is an effective strategy to improve the diagnostic imaging outcome of nanoscale imaging agents in the focal areas. Dual targeting micelles encapsulating superparamagnetic iron oxide were pre...Antibody targeted delivery is an effective strategy to improve the diagnostic imaging outcome of nanoscale imaging agents in the focal areas. Dual targeting micelles encapsulating superparamagnetic iron oxide were prepared from the amphiphilic block copolymer poly（ethylene glycol）-poly（e-caprolactone） （PEG-b-PCL） with different targeting ligands cRGD and scFv-ErbB single chain antibody conjugated to the distal ends of PEG block. The breast cancer animal model was established by subcutaneous injecting the BT474 cells into the BALB/c-nu female nude mice and then employed to assess the potential of the dual ligand targeted magnetic micelles as a novel MRI contrast agent on a 1.5 T clinical MR/scanner. The T2 signal intensity of the tumor in animals receiving the dual ligand targeted magnetic micelles via tail vein decreased more significantly than the single ligand targeted and nontargeted magnetic micelles. These results indicate that the dual ligand targeted magnetic micelles, cRGD/scFv-ErbB-PEG-PCL-SPION, have great potential to act as a new type of effective nanoscale MRI contrast agent for early diagnosis of breast cancer.展开更多
RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer treatment.Meanwhile,an effective approach for siRNA delivery is urgently needed to...RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer treatment.Meanwhile,an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical application.Herein,we constructed a polymeric vector labeled with superparamagnetic iron oxide(SPIO)for magnetic resonance imaging(MRI)visible siRNA delivery.EGFR antibody was also modified to the surface of nanodrug to enhance the delivery effect.Our results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious cytotoxicity.Besides,both in vitro and in vivo studies evidenced the vector could effectively deliver siRNA into tumor cells,exert highly interfering effect,and show potent MR imaging capacity.The study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.展开更多
Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly（ethylene glycol）-block-poly（L-aspar...Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly（ethylene glycol）-block-poly（L-aspartic acid） grafted with diethylenetriamine, lysine and cholic acid （PEG-PAsp（DETA）-Lys-CA2） polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide （LPS）-activated interleukin-6 （IL-6） and monocytes chemotactic protein 1 （MCP-1） expression as well as blocked nuclear factor-rd3 （NF-rd3） signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 （IL-10） and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.展开更多
Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly（aspartic acid...Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly（aspartic acid-butanediamine）-poly（2- （diisopropylamino）ethyl methacrylate） （PAsp（DAB）-PDPA） was synthesized and self-assembled into doxorubicin-loaded micelle, which was further used as a template to form a gold nanoshell. After fitrther modification with poly（ethylene glycol）, the resulting nanoplatform provided good biocompatibility and desirable photo-thermal conversion efficiency to facilitate photothermal therapy. Meanwhile the nanoparticle also exhibited pH sensitivity, which prevented drug loss while circulating in the blood but enabled rapid drug release after endocytosis. An improved effect was achieved with the combination of photothermal therapy and chemotherapy. In addition, systemic delivery of the nanoplatform could be monitored by photoacoustic tomography. Thereby, this multifunctional nanoplatform would be highly potential for the diagnosis and therapy of cancer.展开更多
基金This work was supported by the following funds： National Natural Science Foundation of China （No.30670951） Guangdong Provincial+5 种基金 Natural Science Foundation （No.06021322） Fund of Guangzhou Municipal Scientific Problem-Solving Program （No. 2003 Z 3-E0381） Fund of Guangdong Provincial Scientific Problem-Solving Program （No.2005 B31211002） Guangdong Provincial Government and Ministry of Education Project com- bining project initiation, study and research （No.2009B090300277）.
文摘OBJECTIVE To investigate the effect of polyethylene imine glycol （PEI-PEG）/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. METHODS PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay （mononuclear cell direct cytotoxicity assay）, and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. RESULTS After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was （80.4 ± 5.6）% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to （59.7 ± 3.0）% after siRNA-CD44v6 was inhibited. CONCLUSION PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection e. ciency, less cytotoxicity and an easily alterable vector structure.
文摘A novel kind of copolymer with ABA-type block structure was synthesized by anionic ring-opening polymerization of beta-butyrolactone (beta-BL) in the presence of a PEG-based dicarboxylates as macroinitiators which were prepared by the esterification of aliphatic cyclic anhydride and poly(ethylene glycol) (PEG) oligomers (M-n = 2000, 4000 and 6000) and conversion of potassium dicarboxylates. The resultant copolymers as well as the intermediates were characterized by IR, H-1-NMR and GPC.
基金financially supported by the National Basic Research Program of China (No. 2015CB755500)the Natural Science Foundation of Guangdong Province (No. 2014A030312018)Science and Technology Planning Project of Guangdong Province (No. 2016A020215088)
文摘Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.
基金supported by the 863 Programs of China(No.2009AA03Z310)National Natural Science Foundation of China(Nos.21174166,30973419)+5 种基金the Ph.D.Programs Foundation of Ministry of Education of China(No.20100171110011)the Postdoctoral Foundation(No.201003370)Natural Science Foundation(Nos.9351027501000003,S2011020003140)S&T Programs of Guangdong Province(Nos.2010B031500011,2009B030803003,2009B030801107,2012B031800135)SYSU Projects for Promotion of Key and Emerging Interdisciplinary Researches(10ykjc18)Young Teachers(11lgpy44)
文摘Antibody targeted delivery is an effective strategy to improve the diagnostic imaging outcome of nanoscale imaging agents in the focal areas. Dual targeting micelles encapsulating superparamagnetic iron oxide were prepared from the amphiphilic block copolymer poly（ethylene glycol）-poly（e-caprolactone） （PEG-b-PCL） with different targeting ligands cRGD and scFv-ErbB single chain antibody conjugated to the distal ends of PEG block. The breast cancer animal model was established by subcutaneous injecting the BT474 cells into the BALB/c-nu female nude mice and then employed to assess the potential of the dual ligand targeted magnetic micelles as a novel MRI contrast agent on a 1.5 T clinical MR/scanner. The T2 signal intensity of the tumor in animals receiving the dual ligand targeted magnetic micelles via tail vein decreased more significantly than the single ligand targeted and nontargeted magnetic micelles. These results indicate that the dual ligand targeted magnetic micelles, cRGD/scFv-ErbB-PEG-PCL-SPION, have great potential to act as a new type of effective nanoscale MRI contrast agent for early diagnosis of breast cancer.
基金financially supported by the National Natural Science Foundation of China (Nos. 52173125 and 21805314)the Key Areas Research and Development Program of Guangzhou (No.202007020006)Natural Science Foundation of the Guangdong Province (No. 2021A1515010250)
文摘RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer treatment.Meanwhile,an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical application.Herein,we constructed a polymeric vector labeled with superparamagnetic iron oxide(SPIO)for magnetic resonance imaging(MRI)visible siRNA delivery.EGFR antibody was also modified to the surface of nanodrug to enhance the delivery effect.Our results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious cytotoxicity.Besides,both in vitro and in vivo studies evidenced the vector could effectively deliver siRNA into tumor cells,exert highly interfering effect,and show potent MR imaging capacity.The study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.
基金financially supported by the National Natural Science Foundation of China (No. U1401242)National Basic Research Program of China (No. 2015CB755500)+1 种基金the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2013S086)the Fundamental Research Funds for the Central Universities (Nos. 17lgjc01 and 17lgpy08)
文摘Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly（ethylene glycol）-block-poly（L-aspartic acid） grafted with diethylenetriamine, lysine and cholic acid （PEG-PAsp（DETA）-Lys-CA2） polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide （LPS）-activated interleukin-6 （IL-6） and monocytes chemotactic protein 1 （MCP-1） expression as well as blocked nuclear factor-rd3 （NF-rd3） signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 （IL-10） and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.
基金financially supported by the National Natural Science Foundation of China(No.U1401242)National Basic Research Program of China(No.2015CB755500)+1 种基金Natural Science Foundation of the Guangdong Province(No.2014A030312018)the Fundamental Research Funds for the Central Universities(Nos.17lgjc01 and 17lgpy08)
文摘Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly（aspartic acid-butanediamine）-poly（2- （diisopropylamino）ethyl methacrylate） （PAsp（DAB）-PDPA） was synthesized and self-assembled into doxorubicin-loaded micelle, which was further used as a template to form a gold nanoshell. After fitrther modification with poly（ethylene glycol）, the resulting nanoplatform provided good biocompatibility and desirable photo-thermal conversion efficiency to facilitate photothermal therapy. Meanwhile the nanoparticle also exhibited pH sensitivity, which prevented drug loss while circulating in the blood but enabled rapid drug release after endocytosis. An improved effect was achieved with the combination of photothermal therapy and chemotherapy. In addition, systemic delivery of the nanoplatform could be monitored by photoacoustic tomography. Thereby, this multifunctional nanoplatform would be highly potential for the diagnosis and therapy of cancer.
