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

机译:苯硼酸修饰的中空二氧化硅纳米粒子用于阿霉素的双重反应性递送用于靶向肿瘤治疗

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摘要

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 in vitro. 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. In vivo 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.
机译:这项工作报告了基于中空介孔二氧化硅纳米粒子(HMSNs)的多功能纳米载体,用于靶向肿瘤治疗。将阿霉素(DOX)装入HMSN中,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,将其与细胞色素C共轭的乳糖酸(CytC–LA)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输送系统的成功构建。该系统在体外显示了pH和氧化还原双重反应药物释放行为。载有DOX的HMSNs系统显示出良好的生物相容性,可以被HepG2细胞特异性内吞,并通过诱导细胞凋亡而导致针对肿瘤细胞的高细胞毒性。体内数据(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曙红染色)证明该系统可以高效地将DOX递送至肿瘤部位,并以最小的毒副作用抑制肿瘤的生长。

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