|本期目录/Table of Contents|

[1]陈美惠,丁厚伟,张庆明,等.自组装白蛋白纳米粒作为阿克拉霉素A递送载体[J].医学研究与战创伤救治(原医学研究生学报),2017,19(06):565-569.[doi:10.3969/j.issn.1672-271X.2017.06.002]
　CHEN Mei-hui,DING Hou-wei,ZHANG Qing-ming,et al.Self-assembled albumin nanoparticles as a nanocarrier for aclacinomycin A[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2017,19(06):565-569.[doi:10.3969/j.issn.1672-271X.2017.06.002]
点击复制

自组装白蛋白纳米粒作为阿克拉霉素A递送载体()
分享到62.8K

《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第19卷
期数:
2017年06期
页码:
565-569
栏目:
出版日期:
2017-11-23

文章信息/Info

Title:
Self-assembled albumin nanoparticles as a nanocarrier for aclacinomycin A
作者:
陈美惠1; 丁厚伟1; 张庆明1; 龚光明1; 朱庆2; 王曙东1
作者单位：1.210002南京，南京军区南京总医院制剂科；2.210023南京，南京中医药大学药学院
Author(s):
CHEN Mei-hui1; DING Hou-wei1; ZHANG Qing-ming1; GONG Guang-ming1; ZHU Qing2; WANG Shu-dong1
（1.Department of Pharmaceutical Preparation，Nanjing General Hospital of Nanjing Military Region，PLA，Nanjing 210002，Jiangsu，China；2.College of Pharmacy，Nanjing University of Chinese Medicine，Nanjing 210023，Jiangsu，China）
关键词:
白蛋白; 阿克拉霉素A; 药物递送
Keywords:
Albumin; Aclacinomycin A; Drug delivery
分类号:
R945
DOI:
10.3969/j.issn.1672-271X.2017.06.002
文献标志码:
A
摘要:
目的本研究旨在通过阿克拉霉素（ACM）共价结合氨基氧乙酸（AOA）产生的活性中间体，以降低ACM毒性和提高靶向药物。方法采用三（2-羧乙基）膦（TCEP）作为二硫键断裂分子，通过分子间的“打开-中间-闭合”开关制备人血清白蛋白（HSA）的自组装纳米粒（Nanoparticle，NPs）。结果核磁共振氢谱（1H-NMR）分析表明ACM和AOA之间的结合发生在ACM的酮基(12C)位置。HSA纳米粒（NPs-ACM）负载ACM的载药量为7.4％。NPs-ACM的释放与pH相关。与游离ACM相比，NPs-ACM的细胞毒性和心脏毒性降低。体内研究表明，NPs-ACM对荷瘤小鼠靶向性比游离ACM高4倍（P<0.05）。结论纳米粒NPs-ACM前体药物是理想的ACM肿瘤靶向药物载体。
Abstract:
ObjectiveThis study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin (ACM) by covalently coupling it with amino-oxyacetic acid (AOA) to generate an active intermediate，AOA-ACM.MethodsAOA-ACM was conjugated with self-assembled human serum albumin (HSA) nanoparticles constructed using Tris (2-carboxyethy1) phosphine (TCEP) as disulfide bond breaking molecules.ResultsConjugation between ACM and albumin nanoparticles was found to occur at an ACM ketone site using 1H-NMR. The drug loading efficiency of ACM conjugated with HSA nanoparticles (NPs-ACM) was 7.4% (molar ratio=6:1). The release of NPs-ACM was pH dependent. The cytotoxicity and cardiotoxicity of NPs-ACM were reduced compared with the free ACM. Vivo studies indicated that NPs-ACM exhibited fourfold higher tumor targeting capability on S180-tumor-bearing mice compared with the free ACM (P<0.05).ConclusionThe NPs-ACM prodrug is ideal tumor targeting drug carriers for ACM

参考文献/References:

[1]Nitiss JL，Pourquier P，Pommier Y. Aclacinomycin A stabilizes topoisomerase I covalent complexes[J]. Cancer Res，1997，57(20): 4564-4569.
[2]Ariji F，Shida K，Konno K，et al. Cardiotoxic study of aclacinomycin A. Subacute cardiotoxic effect of aclacinomycin A in rats (author’s transl) [J].Jpn J Antibiot，1980，33(3): 281-293.
[3]章磊,流小舟,孙畅,等.多途径靶向给药系统在骨肉瘤治疗中的研究进展[J]. 东南国防医药，2016，18（6）632-635.
[4]Shiokawa T，Hattori Y，Kawano K，et al. Effect of polyethylene glycol linker chain length of folate-linked microemulsions loading aclacinomycin A on targeting ability and antitumor effect in vitro and in vivo[J]. Clin Cancer Res，2005,11(5): 2018-2025.
[5]Wang J，Maitani Y，Takayama K. Antitumor effects and pharmacokinetics of aclacinomycin A carried by injectable emulsions composed of vitamin E，cholesterol，and PEG-lipid[J]. J Pharm Sci，2002，91(4):1128-1134.
[6]Jiang XH，Liao GT，Huang GQ，et al. The antihepatoma effect of lyophilized aclacinomycin A polyisobutylcyanoacrylate nanoparticles in vitro and in vivo[J].Yao Xue Xue Bao，1995，30(3):179-183.
[7]Wohl AR，Michel AR，Kalscheuer S,et al. Silicate esters of paclitaxel and docetaxel: synthesis，hydrophobicity，hydrolytic stability，cytotoxicity，and prodrug potential[J].J Med Chem，2014，57 (6)：2368-2379.
[8]Israel LL，Kovalenko EI，Boyko AA，et al.Towards hybrid biocompatible magnetic rHuman serum albumin-based nanoparticles: use of ultra-small (CeLn)3/4+ cation-doped maghemite nanoparticles as functional shell[J]. Nanotechnology，2015，26(4):045601.doi: 10.1088/0957-4484/26/4/045601.
[9]Kobayashi H，Watanabe R，Choyke PL. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? [J] Theranostics，2014，4(1): 81-89.
[10]Wilson B，Ambika TV，Patel RD，et al.Nanoparticles based on albumin: preparation，characterization and the use for 5-flurouracil delivery[J].Int J Biol Macromol，2012， 51（5）： 874-878.
[11]Subia B，Kundu SC. Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers[J]. Nanotechnology，2013，24(3)：035103. doi: 10.1088/0957-4484/24/3/035103.
[12]Kastl R，Wennemers H. Peptide-catalyzed stereoselective conjugate addition reactions generating all-carbon quaternary stereogenic centers[J].Angew Chem Int Ed Engl，2013，52 (28): 7228-7732.
[13]Kitamura I，Oki T，Inui T. A sensitive analytical method for aclacinomycin A and its analogs by thin-layer chromatography and fluorescence scanning[J]. J Antibiot (Tokyo)，1978,31(9):919-922.
[14]龚光明，陈美惠，王曙东. 人血浆蛋白多烯紫杉醇纳米粒子的自组装及对肿瘤的靶向性[J].东南国防医药，2016，18（5）468-471.

相似文献/References:

备注/Memo

备注/Memo:
基金项目：国家自然科学基金（31671026）
更新日期/Last Update: 2017-11-20