韩笑;李玉林;张怡青;于茵茵;王旭东;吴玉彬;王晓军;朱彦霞;李三强;王云龙;

• 1:河南科技大学医学院
• 2:河南省生物工程技术研究中心
• 3:洛阳市中心医院
• 4:郑州职业技术学院生物工程系

摘要(Abstract)：

通过重组的乙肝核心蛋白病毒样颗粒（HBc-VLPs）对阿霉素进行包封已经被证实有良好的靶向缓释效果，但是载药量和稳定性方面仍待提升，本文基于β-环糊精（β-CD）建立一种有效的HBc-VLPs-β-CD-DOX制备方法，利用高效液相、粒径、透射电镜等方式评价HBc-VLPs-β-CD-DOX的表征、载药量、稳定性以及乳腺癌细胞的抗肿瘤活性。结果显示，HBc-VLPs-β-CD-DOX呈球形，粒径为（30±2）nm左右，大小形态均一，其载药量可达250μg/mL，相较于HBc-DOX-VLPs有明显提升，粒径结果显示HBc-VLPs-β-CD-DOX在4°C的环境下可存放30d，动态透析法显示HBc-VLPs-β-CD-DOX在生理状态下有较好的稳定性，DOX的泄漏率不到1%，细胞毒性结果显示，HBc-VLPs-β-CD-DOX对于4T1细胞的有较好的杀伤作用，IC_(50)可达到1.128μg/mL。研究结果表明，HBc-VLPs-β-CD-DOX制备成功并建立了高效的包封方法，表现出良好的保存稳定性和生理稳定性以及对肿瘤细胞的杀伤效果，是一种非常有前景的纳米靶向药物。

关键词(KeyWords)： HBc-VLPs;纳米载体;靶向药物;肿瘤治疗

Abstract:

Keywords:

基金项目(Foundation): 河南省中原学者项目（项目号：192101510001）,题目：RGD-HBc-NS5A病毒样颗粒诊断和治疗药物靶向给药系统研究~~

作者(Authors): 韩笑;李玉林;张怡青;于茵茵;王旭东;吴玉彬;王晓军;朱彦霞;李三强;王云龙;

DOI: 10.13242/j.cnki.bingduxuebao.004260

参考文献(References)：

• [1] Rybka J D, Mieloch A A, Plis A, Pyrski M, Pniewski T, Giersig M. Assembly and characterization of HBc derived virus-like particles with magnetic core[J].Nanomaterials(Basel),2019,9(2):155.
• [2] Jiang D D, Wang Y L, Li Y L, Zhang Y Q. RGDmodified virus-like particles for delivery of ICG targeting tumors[J]. Chinese Journal of Biological Engineering.2020,40(07):22-29.
• [3] Li F, Zhao Y, Mao C,Kong Y, Ming X. RGDmodified albumin nanoconjugates for targeted delivery of a porphyrin photosensitizer[J]. Mol Pharm,2017,14(8):2793–2804.
• [4] Shan W, Zhang D, Wu Y, Lv X, Hu B, Zhou X, Ye S, Bi S, Ren L, Zhang X. Modularized peptides modified HBc virus-like particles for encapsulation and tumor-targeted delivery of doxorubicin. Nanomedicine,2018,14(3):725-734.
• [5] Zhang L, Chen H. Construction and performance evaluation of positive and negative charge modified hepatitis B virus-like particles[J]. Journal of Tianjin University(Natural Science and Engineering Technology Edition),2020,53(05):450-458.
• [6] Li Q Y, Lou L N, Long X L, Yang Y, Xu Y L.Research progress of β-cyclodextrin and its derivatives as drug carriers[J].Modern Salt Chemical Industry,2020,47(04):1-2.
• [7] Yan M, Cai A, Li J, Xin M, Liu M, Wang C, Wei G.Preparation of β-CD-DPPE-Dox nanomedicine and its'application as the anticancer and antitumor drug[J]. Sci Rep, 2019, 9(1):13670.
• [8] Niikura K, Sugimura N, Musashi Y, Mikuni S,Matsuo Y, Kobayashi S, Nagakawa K, Takahara S,Takeuchi C, Sawa H, Kinjo M, Ijiro K. Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells[J]. Mol Biosyst, 2013,9(3):501-507.
• [9] Xu D. Hepatitis B virus core protein nanocages loaded with quercetin for the treatment and MRI diagnosis of liver fibrosis in mice[D].Xiamen University,2019.
• [10]Yang T, Du G, Cui Y,Yu R, Hua C, Tian W, Zhang Y. pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancertargeted therapy[J]. Int J Nanomedicine, 2019,14:1997–2010.
• [11]Rybka J D, Mieloch A A, Plis A, Pyrski M, Pniewski T, Giersig M. Assembly and characterization of hbc derived virus-like particles with magnetic core[J].Nanomaterials(Basel, Switzerland),2019, 9(2):155.
• [12]Han H S, Lee J, Kim H R,Chae SY, Kim M,Saravanakumar G, Yoon H Y, You D G, Ko H, Kim K, Kwon I C, Park J C, Park J H. Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin:mineralization and its effect on tumor targetability in vivo[J]. J Control Release,2013,168(2):105–114.
• [13]Wang Y, Bi K, Shu J,Liu X, Xu J, Deng G.Ultrasound-controlled DOX-SiO2 nanocomposites enhance the antitumour efficacy and attenuate the toxicity of doxorubicin[J]. Nanoscale, 2019,11(10):4210-4218.
• [14]Yan J, Song B, Hu W, Meng Y, Niu F, Han X, Ge Y, Li N. Antitumor effect of GO-PEG-DOX complex on EMT-6 mouse breast cancer cells[J]. Cancer Biother Radiopharm, 2018,33(4):125-130.
• [15]Lv S, Tang Z, Song W, Zhang D, Li M, Liu H,Cheng J, Zhong W, Chen X. Inhibiting solid tumor growth in vivo by non-tumor-penetrating nanomedicine[J].Small,2017,13(12).