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用于阿霉素双响应递送以进行靶向肿瘤治疗的苯基硼酸修饰的中空二氧化硅纳米颗粒

Phenylboronic acid-modified hollow silica nanoparticles for dual-responsive delivery of doxorubicin for targeted tumor therapy.

作者信息

Huang Ling, Zhang Qingfeng, Dai Liangliang, Shen Xinkun, Chen Weizhen, Cai Kaiyong

机构信息

Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.

出版信息

Regen Biomater. 2017 Mar;4(2):111-124. doi: 10.1093/rb/rbw045. Epub 2017 Jan 11.

Abstract

This work reports a multifunctional nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for targeting tumor therapy. Doxorubicin (DOX) was loaded into HMSNs and blocked with cytochrome C conjugated lactobionic acid (CytC-LA) via redox-cleavable disulfide bonds and pH-disassociation boronate ester bonds as intermediate linkers. The CytC-LA was used both as sealing agent and targeting motif. A series of characterizations demonstrated the successful construction of the drug delivery system. The system demonstrated pH and redox dual-responsive drug release behavior . The DOX loading HMSNs system displayed a good biocompatibility, which could be specifically endocytosed by HepG2 cells and led to high cytotoxicity against tumor cells by inducing cell apoptosis. data (tumor volume, tumor weight, terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining) proved that the system could deliver DOX to tumor site with high efficiency and inhibit tumor growth with minimal toxic side effect.

摘要

这项工作报道了一种基于中空介孔二氧化硅纳米颗粒(HMSNs)的多功能纳米载体用于靶向肿瘤治疗。将阿霉素(DOX)载入HMSNs,并通过氧化还原可裂解的二硫键和pH解离硼酸酯键作为中间连接体,用细胞色素C偶联乳糖酸(CytC-LA)进行封闭。CytC-LA既用作密封剂又用作靶向基序。一系列表征证明了药物递送系统的成功构建。该系统表现出pH和氧化还原双重响应的药物释放行为。载入DOX的HMSNs系统显示出良好的生物相容性,其可被HepG2细胞特异性内吞,并通过诱导细胞凋亡对肿瘤细胞产生高细胞毒性。数据(肿瘤体积、肿瘤重量、末端脱氧核苷酸转移酶dUTP缺口末端标记以及苏木精和伊红染色)证明该系统能够高效地将DOX递送至肿瘤部位,并以最小的毒副作用抑制肿瘤生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c34/6371689/a89060685832/rbw045f1.jpg

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