载阿霉素金纳米粒的制备和细胞毒性研究
投稿时间:2023-08-21  修订日期:2023-10-19  点此下载全文
引用本文:许子艺,孙雨菡,樊莉,卢光照,张鹰楠,张翮.载阿霉素金纳米粒的制备和细胞毒性研究[J].药学实践杂志,2024,42(2):73~77,81
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作者单位E-mail
许子艺 海军军医大学药学系药剂学教研室, 上海 200433  
孙雨菡 海军军医大学药学系药剂学教研室, 上海 200433  
樊莉 海军军医大学药学系药剂学教研室, 上海 200433  
卢光照 海军军医大学药学系药剂学教研室, 上海 200433  
张鹰楠 海军军医大学药学系药剂学教研室, 上海 200433  
张翮 海军军医大学药学系药剂学教研室, 上海 200433 wwzh22@126.com 
中文摘要:目的 构建载阿霉素(DOX)的甲氧基聚乙二醇(mPEG)修饰的金纳米粒AuNPs-mPEG@DOX,以降低DOX的毒副作用。方法 制备AuNPs-mPEG@DOX,通过粒径、电位和紫外可见光吸收光谱(UV-Vis)进行表征。考察连接巯基的DOX(HS-DOX)投药浓度对AuNPs-mPEG@DOX吸附率和载药量的影响。建立未吸附HS-DOX含量测定的高效液相色谱法(HPLC),对专属性、线性、精密度、稳定性和加样回收率进行考察。采用CCK-8法检测AuNPs-mPEG@DOX对MCF-10A和MCF-7细胞的毒性作用。结果 成功制备了AuNPs-mPEG@DOX,粒径为(46.12±0.49) nm,电位为(18.60±1.51) mV,最大吸收波长为530 nm。建立了可用于检测AuNPs-mPEG@DOX未吸附HS-DOX含量的HPLC方法,测定最佳投药浓度11.18 μg/ml,HS-DOX条件下的吸附率为(9.21±2.88)%,载药量为(2.01±0.62)%。细胞毒性实验表明AuNPs-mPEG@DOX可明显降低DOX对正常乳腺细胞的毒副作用;DOX在≥4.75 μmol/L时,AuNPs-mPEG@DOX与游离DOX对乳腺肿瘤细胞的细胞毒性作用一致。结论 AuNPs-mPEG@DOX可有效降低DOX的毒副作用,为后续AuNPs连接药物降低其毒副作用的研究提供参考。
中文关键词:金纳米粒  阿霉素  乳腺肿瘤  毒副作用
 
Preparation and cytotoxicity of doxorubicin-containing gold nanoparticles
Abstract:Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.
keywords:gold nanoparticles  doxorubicin  breast tumor  toxicity
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