Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of ...Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area,we evaluated the hollow polydopamine nanoparticles(HPDA NPs),in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect.Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility.Results of qRT-PCR,ALP,and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells(rBMSCs)in vitro.Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo,especially tacrolimus.These results suggest that the HPDA NPs,the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability,have good prospect to treat the bone defect in future clinical practice.展开更多
Delivery systems based on nanoparticles(NPs)have shown great potential to reduce side effects and improve the therapeutic efficacy.Herein,we report the one-pot synthesis of poly(ethylene glycol)-mediated zeolitic imid...Delivery systems based on nanoparticles(NPs)have shown great potential to reduce side effects and improve the therapeutic efficacy.Herein,we report the one-pot synthesis of poly(ethylene glycol)-mediated zeolitic imidazolate framework-8(ZIF-8)NPs for the co-delivery of an anticancer drug(i.e.,doxorubicin)and a cell penetrating peptide containing histidine and arginine(i.e.,H4 R4)to improve the efficacy of therapeutic delive ry.The cargo-encapsulated ZIF-8 NPs are pH-responsive,which are stable at neutral pH and degradable at acidic pH to release the encapsulated cargos.The released H4 R4 can help for endosome/lysosome escape to enhance the cytotoxicity of the encapsulated drugs.In vivo studies demonstrate that the co-delivery of doxo rubicin and H4 R4 peptides can efficiently inhibit tumor growth without significant side effects.The reported strategy provides a new perspective on the design of drug delivery systems and brings more opportunities for biomedical applications.展开更多
基金supported by grants from the National Key Research and Development Program of China(2016YFC1102800)the Natural Science Foundation of China(81870741,21774045,and 81920108012)Program for JLU Science and Technology Innovative Research Team(2017TD-11)。
文摘Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration.They,however,still face disadvantages of high toxicity,low biocompatibility,and low drug-load capacity.In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area,we evaluated the hollow polydopamine nanoparticles(HPDA NPs),in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect.Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility.Results of qRT-PCR,ALP,and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells(rBMSCs)in vitro.Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo,especially tacrolimus.These results suggest that the HPDA NPs,the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability,have good prospect to treat the bone defect in future clinical practice.
基金supported by the National Natural Science Foundation of China(Nos.21872085 and 21902088)the Project for Scientific Research Innovation Team of Young Scholar in Colleges and Universities of Shandong Province(No.2020KJC001)。
文摘Delivery systems based on nanoparticles(NPs)have shown great potential to reduce side effects and improve the therapeutic efficacy.Herein,we report the one-pot synthesis of poly(ethylene glycol)-mediated zeolitic imidazolate framework-8(ZIF-8)NPs for the co-delivery of an anticancer drug(i.e.,doxorubicin)and a cell penetrating peptide containing histidine and arginine(i.e.,H4 R4)to improve the efficacy of therapeutic delive ry.The cargo-encapsulated ZIF-8 NPs are pH-responsive,which are stable at neutral pH and degradable at acidic pH to release the encapsulated cargos.The released H4 R4 can help for endosome/lysosome escape to enhance the cytotoxicity of the encapsulated drugs.In vivo studies demonstrate that the co-delivery of doxo rubicin and H4 R4 peptides can efficiently inhibit tumor growth without significant side effects.The reported strategy provides a new perspective on the design of drug delivery systems and brings more opportunities for biomedical applications.
