VanHandel Michelle, Alizadeh Darya, Zhang Leying, Kateb Babak, Bronikowski Michael, Manohara Harish, Badie Behnam
Division of Neurosurgery, City of Hope Medical Center and Beckman Research Institute, Duarte, CA 91010, USA.
J Neuroimmunol. 2009 Mar 31;208(1-2):3-9. doi: 10.1016/j.jneuroim.2008.12.006. Epub 2009 Jan 31.
Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and gene delivery into biological systems. To evaluate potential application of this technology for brain tumor therapy, we studied uptake and toxicity of multi-walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h of a single intratumoral injection of labeled MWCNTs (5 microg), nearly 10-20% of total cells demonstrated CNT internalization. Most CNT uptake, however, occurred by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT-positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT-positive. Despite a transient increase in inflammatory cell infiltration into both normal and tumor-bearing brains following MWCNT injection, no significant toxicity was noted in mice, and minor changes in tumor cytokine expression were observed. This study suggests that MWCNTs could potentially be used as a novel and non-toxic vehicle for targeting MP in brain tumors.
碳纳米管(CNT)正在成为用于将药物和基因递送至生物系统的新型纳米载体家族。为了评估该技术在脑肿瘤治疗中的潜在应用,我们在GL261小鼠颅内胶质瘤模型中研究了多壁碳纳米管(MWCNT)的摄取和毒性。在单次瘤内注射标记的MWCNT(5微克)后24小时内,近10 - 20%的总细胞表现出CNT内化。然而,大多数CNT摄取是由肿瘤相关巨噬细胞(MP)发生的,其占大多数(75%)的MWCNT阳性细胞。注射后24小时内,近30%的肿瘤MP变为MWCNT阳性。尽管MWCNT注射后正常脑和荷瘤脑中炎性细胞浸润有短暂增加,但在小鼠中未观察到明显毒性,并且观察到肿瘤细胞因子表达有轻微变化。这项研究表明,MWCNT可能潜在地用作靶向脑肿瘤中MP的新型无毒载体。