Li Nannan, Zhao Qian, Shu Chang, Ma Xiaona, Li Ruixin, Shen Hongjun, Zhong Wenying
Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, PR China.
Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, PR China; Key Laboratory for Drug Quality Control and Pharmacovigilance of Ministry of Education, China Pharmaceutical University, Nanjing 210009, PR China.
Int J Pharm. 2015 Jan 30;478(2):644-54. doi: 10.1016/j.ijpharm.2014.12.015. Epub 2014 Dec 12.
Oxidized single-wall carbon nanohorns (oxSWNHs) have shown great potential in drug delivery. The purpose of this study was to design an effective targeted drug delivery system (DDS) based on oxSWNHs, which could carry high dose of drug to tumor sites and improve the therapeutic efficacy with less adverse effects. OxSWNHs incorporated the anticancer drug vincristine (VCR) via physical adsorption, then wrapped DSPE-PEG-IGF-IR monoclonal antibody (mAb) through an amide liker to obtain the drug delivery system, VCR@oxSWNHs-PEG-mAb. The in vitro release behavior study indicated that the DDS had good sustained release and the cumulative release of VCR was 80% at 144h. Compared with free VCR, the tumor targeting drug delivery efficiently enhanced the cytotoxicity in cultured MCF-7 cells in vitro, and afforded higher antitumor efficacy without obvious toxic effects to normal organs in tumor mice in vivo. In addition, the targeted DDS could reduce the toxicity of VCR to the living mice. This study demonstrated that VCR@oxSWNHs-PEG-mAb might be promising for high treatment efficacy with minimal side effects in future cancer therapy.
氧化单壁碳纳米角(oxSWNHs)在药物递送方面已显示出巨大潜力。本研究的目的是基于oxSWNHs设计一种有效的靶向药物递送系统(DDS),该系统能够将高剂量药物输送到肿瘤部位,并在减少不良反应的情况下提高治疗效果。oxSWNHs通过物理吸附结合抗癌药物长春新碱(VCR),然后通过酰胺连接体包裹DSPE-PEG-IGF-IR单克隆抗体(mAb)以获得药物递送系统VCR@oxSWNHs-PEG-mAb。体外释放行为研究表明,该DDS具有良好的缓释性能,VCR在144小时的累积释放率为80%。与游离VCR相比,肿瘤靶向药物递送在体外有效增强了对培养的MCF-7细胞的细胞毒性,并且在体内对荷瘤小鼠的正常器官没有明显毒性作用的情况下提供了更高的抗肿瘤疗效。此外,靶向DDS可以降低VCR对活体小鼠的毒性。本研究表明,VCR@oxSWNHs-PEG-mAb在未来癌症治疗中可能有望实现高治疗效果且副作用最小。