Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone ...Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.展开更多
Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially sy...Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially synthesized nanocarriers still faces several challenges, including rapid clearance from blood circulation and limited capability of overcoming multiple physiological barriers, which hamper the clinical application of nanoparticle-based therapies. Since leukocytes(including monocytes/macrophages,neutrophils, dendritic cells and lymphocytes) target tumors and can migrate across physiological barriers,leukocytes are increasing utilized as carriers to transfer nanoparticles to tumors. In this review we specifically focus on the molecular and cellular mechanisms of leukocytes that can be exploited as a vehicle to deliver nanoparticles to tumors and summarize the latest research on how leukocytes can be harnessed to improve therapeutic end-points. We also discuss the challenges and opportunities of this leukocyte-derived nanoparticle drug delivery system.展开更多
The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membr...The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membrane receptors to recognize the designed ligands,and provokes the off-target toxicity and rapid clearance of NPs in vivo.Herein,we report a novel dihydroartemisinin(DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E(apoE)on the NPs surface.The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA(PPD)NPs circulation capability in blood,facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention(EPR)effect and low-density lipoprotein receptor(LDLr)-mediated target transport,and ultimately improve the in vivo antitumor activity.Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.展开更多
Tumor micro-environment responsive drug delivery systems （DDSs） have been developed as a potential approach to reduce the side effects of cancer chemotherapy. Glutathione （GSH） has been supposed to the most signif...Tumor micro-environment responsive drug delivery systems （DDSs） have been developed as a potential approach to reduce the side effects of cancer chemotherapy. Glutathione （GSH） has been supposed to the most significant signal of the difference between the normal tissue and the tumor cells, besides the media pH and temperature. In recent years, the reduction-responsive DDSs have attracted more and more attention for delivery of anti-cancer drugs, based on such physiological signal. Among them, disulfide bond-containing polymers have been designed as the main tool for the purpose. The recent progress in the synthesis strategies for the disulfide bond- containing polymer-based DDS is focused in the present review.展开更多
In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous em...In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.展开更多
基金supported by the National Natural Science Foundation of China(#81872220 and#81703437)Xinjiang Uygur Autonomous Region Science and Technology Support Project(#2020E0290)+4 种基金Basic Public Welfare Research Project of Zhejiang Province(#LGF18H160034,LGC21B050011 and#LGF20H300012),Science and Technology Bureau of Jiaxing(2020AY10021)Key Research and Development and Transformation project of Qinghai Province(2021-SF-C20)Dutch Cancer Foundation(KWF project#10666)a Zhejiang Provincial Foreign Expert Program Grant,Zhejiang Provincial Key Natural Science Foundation of China(#Z20H160031)and Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research,and“Innovative Jiaxing·Excellent Talent Support Program”-Top Talents in Technological Innovation.
文摘Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.
基金supported by National Natural Science Foundation of China (Nos. 81673019, 81690263 and 81373353)"Shu Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (15SG14)
文摘Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially synthesized nanocarriers still faces several challenges, including rapid clearance from blood circulation and limited capability of overcoming multiple physiological barriers, which hamper the clinical application of nanoparticle-based therapies. Since leukocytes(including monocytes/macrophages,neutrophils, dendritic cells and lymphocytes) target tumors and can migrate across physiological barriers,leukocytes are increasing utilized as carriers to transfer nanoparticles to tumors. In this review we specifically focus on the molecular and cellular mechanisms of leukocytes that can be exploited as a vehicle to deliver nanoparticles to tumors and summarize the latest research on how leukocytes can be harnessed to improve therapeutic end-points. We also discuss the challenges and opportunities of this leukocyte-derived nanoparticle drug delivery system.
基金Supported by Anhui University of Chinese Medicine Foundation(No.2019zrzd13)the Key Project of Anhui Province Department of Education(No.KJ2019A0471)+1 种基金the Key Project of Liaoning Province Department of Education(No.2017LZD03)the National Nature Science Foundation of China(Nos.81473164,81703451,81873019 and 81873351,U1608283).
文摘The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membrane receptors to recognize the designed ligands,and provokes the off-target toxicity and rapid clearance of NPs in vivo.Herein,we report a novel dihydroartemisinin(DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E(apoE)on the NPs surface.The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA(PPD)NPs circulation capability in blood,facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention(EPR)effect and low-density lipoprotein receptor(LDLr)-mediated target transport,and ultimately improve the in vivo antitumor activity.Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.
基金Acknowledgements This project was granted financial support from the National Natural Science Foundation of China （Grant No. 20904017） and the Program for New Century Excellent Talents in University （Grant No. NCET-09-0441）.
文摘Tumor micro-environment responsive drug delivery systems （DDSs） have been developed as a potential approach to reduce the side effects of cancer chemotherapy. Glutathione （GSH） has been supposed to the most significant signal of the difference between the normal tissue and the tumor cells, besides the media pH and temperature. In recent years, the reduction-responsive DDSs have attracted more and more attention for delivery of anti-cancer drugs, based on such physiological signal. Among them, disulfide bond-containing polymers have been designed as the main tool for the purpose. The recent progress in the synthesis strategies for the disulfide bond- containing polymer-based DDS is focused in the present review.
基金financially supported by the European Erasmus program
文摘In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.
