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
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.
