An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitiv...An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction,then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs,and nanoparticles were formed through self-assembling.Moreover,the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry(UV),nuclear magnetic resonance spectroscopy(^(1)H-NMR),fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS),and transmission electron microscopy(TEM).The mean diameter of the self-assembled nanoparticles is 165 nm,while the morphology is a relatively uniform spherical shape.Moreover,these DOXloaded nanoparticles showed pH-triggered drug release behavior.Compared with free DOX,CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells.The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.展开更多
This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined...This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined the nanodrug’s therapeutic efficacy.An integral analytical method was used to characterize the structure of MPEG-PCL.The single factor method and orthogonal test were utilized to investigate the optimum preparation process.The morphology and average size of the OMT-NPs were analyzed by transmission electron microscopy and Zetasizer.CCK-8 assay and confocal fluorescent microscope were used to study the inhibitory effect on SGC-7901 gastric cancer cells.The average size of nanoparticles was 95.86±1.54 nm.The maximum encapsulation efficiency of OMT was 46.84±4.37%,while the drug loading content was 8.89±1.09%.The cumulative release of nanoparticles was 73.07±1.5%,inspected through dynamic dialysis in vitro.Compared with free OMT,OMT-NPs showed enhanced cytotoxic effects in SGC-7901 cells.The nanoparticles could efficiently deliver the OMT into the cancer cells and release it.The OMT delivery system prepared in this paper provides a potential platform for the treatment of gastric cancer..展开更多
基金Funded by the Industrial Technology Research Institute of Hubei Provincial Department of Science and Technology(No.2020DEB012)the Hubei Provincial Department of Science and Technology Support Enterprise Technology Innovation Development Project(No.2021BAB119)。
文摘An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction,then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs,and nanoparticles were formed through self-assembling.Moreover,the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry(UV),nuclear magnetic resonance spectroscopy(^(1)H-NMR),fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS),and transmission electron microscopy(TEM).The mean diameter of the self-assembled nanoparticles is 165 nm,while the morphology is a relatively uniform spherical shape.Moreover,these DOXloaded nanoparticles showed pH-triggered drug release behavior.Compared with free DOX,CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells.The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.
基金Funded by the National Natural Science Foundation of China(No.51273156)the Health Commission of Hubei Province Scientific Research Project(No.WJ2019H275)。
文摘This paper provides a new treatment for gastric cancer with a new OMT delivery system.We synthesized MPEG-PCL,an amphiphilic polymer,to construct a nanoparticle encapsulated OMT by pH gradient method,and then examined the nanodrug’s therapeutic efficacy.An integral analytical method was used to characterize the structure of MPEG-PCL.The single factor method and orthogonal test were utilized to investigate the optimum preparation process.The morphology and average size of the OMT-NPs were analyzed by transmission electron microscopy and Zetasizer.CCK-8 assay and confocal fluorescent microscope were used to study the inhibitory effect on SGC-7901 gastric cancer cells.The average size of nanoparticles was 95.86±1.54 nm.The maximum encapsulation efficiency of OMT was 46.84±4.37%,while the drug loading content was 8.89±1.09%.The cumulative release of nanoparticles was 73.07±1.5%,inspected through dynamic dialysis in vitro.Compared with free OMT,OMT-NPs showed enhanced cytotoxic effects in SGC-7901 cells.The nanoparticles could efficiently deliver the OMT into the cancer cells and release it.The OMT delivery system prepared in this paper provides a potential platform for the treatment of gastric cancer..
