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
本研究以石榴皮和百香果果皮为原料,进行石榴皮及百香果果皮(Pomegranate and passion fruit peel,PPFP)复合发酵饮料的研制,通过单因素及响应面试验优化复合饮料发酵工艺条件,并探讨其对小鼠运动耐力的影响。结果表明:复合饮料最佳发...本研究以石榴皮和百香果果皮为原料,进行石榴皮及百香果果皮(Pomegranate and passion fruit peel,PPFP)复合发酵饮料的研制,通过单因素及响应面试验优化复合饮料发酵工艺条件,并探讨其对小鼠运动耐力的影响。结果表明:复合饮料最佳发酵工艺条件为:石榴皮汁添加量20%、百香果果皮汁添加量24%、发酵时间36 h、发酵温度40℃,感官评分为(94.05±1.85)分,活菌数为(8.5±0.2)lg(CFU/g),在此发酵工艺条件下研制的复合饮料色泽均一,具有石榴皮混合发酵后的独特风味,酸甜适口,无明显分层现象。小鼠试验结果表明:与空白对照组相比,低、中、高剂量组可显著延长小鼠负重力竭游泳时间,小鼠肝糖原和肌糖原储备显著增加,显著降低小鼠血清中乳酸和尿素氮含量(P<0.05)。说明PPFP复合发酵饮料有利于提高小鼠机体运动耐力。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.
文摘本研究以石榴皮和百香果果皮为原料,进行石榴皮及百香果果皮(Pomegranate and passion fruit peel,PPFP)复合发酵饮料的研制,通过单因素及响应面试验优化复合饮料发酵工艺条件,并探讨其对小鼠运动耐力的影响。结果表明:复合饮料最佳发酵工艺条件为:石榴皮汁添加量20%、百香果果皮汁添加量24%、发酵时间36 h、发酵温度40℃,感官评分为(94.05±1.85)分,活菌数为(8.5±0.2)lg(CFU/g),在此发酵工艺条件下研制的复合饮料色泽均一,具有石榴皮混合发酵后的独特风味,酸甜适口,无明显分层现象。小鼠试验结果表明:与空白对照组相比,低、中、高剂量组可显著延长小鼠负重力竭游泳时间,小鼠肝糖原和肌糖原储备显著增加,显著降低小鼠血清中乳酸和尿素氮含量(P<0.05)。说明PPFP复合发酵饮料有利于提高小鼠机体运动耐力。