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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2023 11

Page:

1973-1979

Research Field:

Publishing date:

Info

Title:

Hyaluronic acid-modified pH-responsive doxorubicin nano-delivery system targeting multiple myeloma in vitro

Author(s):

YAN Jiahua¹; 2; 3; ZHANG Chuanmin²; 3; XIAO Bolian²; 3; WANG Lijuan²; 3; 4; 5; 6

Keywords:

nano-delivery; doxorubicin; active targeting ability; pH-responsive controlled release; CD44

PACS:

R733.3

DOI:

10.3969/j.issn.1672-4992.2023.11.001

Abstract:

Objective:To construct a pH-responsive nano-delivery for specific targeting multiple myeloma cells to realize the controlled release of chemotherapeutic drug DOX.Methods:Doxorubicin targeted nano-delivery system (DOX-HA-NDS)was designed and constructed by using DSPE-PEOz,DOTAP and HA-PEG2000-DSPE (HA) for delivery of the model drug doxorubicin (DOX).The particle size and Zeta potential of DOX-HA-NDS were analyzed by using nanoparticle size analyzer.The encapsulation efficiency and drug loading of DOX-HA-NDS were detected by microplate reader.The drug release behavior of DOX-HA-NDS in vitro(pH 5.0 and pH 7.4) was studied by dialysis method.The cell uptake of DOX-HA-NDS was detected by flow cytometry.The toxicity of blank nano-delivery system (Blank-HA-NDS) and the inhibitory effect of DOX-HA-NDS on cell proliferation were evaluated by CCK-8 assay.Results:The obtained DOX-HA-NDS with particle size of (193.1±5.0) nm,Zeta potential of (-41.1±2.0) mV,the high encapsulation efficiency of 93% and 90%,and the drug loading efficiency of 32.76% and 32% with centrifugation and dialysis method,could maintain its stability at least 6 months at 4 ℃.At pH 7.4,the cumulative DOX release from DOX-HA-NDS was slow and the cumulative release rate for DOX-HA-NDS was only 30% at 6 h,while at pH 5.0,the DOX release fraction increased significantly and the cumulative release rate for DOX-HA-NDS was up to 97% within 6 h,indicating DOX-HA-NDS has pH-responsive controlled release behavior.The results of cell uptake test showed that compared with DOX-NDS,nano-delivery system modified with hyaluronic acid (DOX-HA-NDS) could target tumor cells more effectively.The results of in vitro antitumor activity showed that the blank nano-delivery system(Blank-HA-NDS)had low cytotoxicity.At the same time,compared with Free DOX and DOX-NDS,DOX-HA-NDS had the strongest cell growth inhibition on human multiple myeloma cells (ARH-77).Conclusion:The constructed DOX-HA-NDS with high encapsulation efficiency,active targeting ability and pH-responsive controlled release behavior can improve the delivery efficiency of DOX,resulting in more efficient cell growth inhibition for ARH-77 cells.

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Memo

Memo:

National Natural Science Foundation of China(No.81402353）；国家自然科学基金项目(编号：81402353)；中国博士后科学基金(编号：2015M580594)；山东省重点研发计划(编号：2018GSF118035)；徐州医科大学附属医院发展基金(编号：XYFM2020016)

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