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脂质体介导的神经母细胞瘤治疗

Liposome-mediated therapy of neuroblastoma.

作者信息

Di Paolo Daniela, Loi Monica, Pastorino Fabio, Brignole Chiara, Marimpietri Danilo, Becherini Pamela, Caffa Irene, Zorzoli Alessia, Longhi Renato, Gagliani Cristina, Tacchetti Carlo, Corti Angelo, Allen Theresa M, Ponzoni Mirco, Pagnan Gabriella

机构信息

Experimental Therapy Unit, Laboratory of Oncology, G. Gaslini Children's Hospital, Genoa, Italy.

出版信息

Methods Enzymol. 2009;465:225-49. doi: 10.1016/S0076-6879(09)65012-6.

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. Despite of aggressive treatment strategies, the 5-year survival rate for metastatic disease is still less than 60% and, consequently, novel therapeutic approaches are needed. For increasing the therapeutic index of anticancer drugs, while reducing side effects, one of the most promising strategies in modern chemotherapy is based on the development of innovative drug delivery systems, such as liposomes. "Anticancer drug"-loaded liposomes have demonstrated enhanced ability to target to the affected area, as well as increased antitumor efficacy compared to conventional drugs. Liposomes tend to extravasate preferentially and to accumulate into tumor interstitial fluids, due to the defective structure of the new angiogenic vessels within the tumor masses. This inherent tumor selectivity can be increased further by coupling tumor-specific antibodies or other targeting moieties to the surface of the lipid envelope. Here, we describe the methodology used in these studies, as well as the antitumor results obtained by the use of several "anticancer drugs," encapsulated into antibody- and peptide-targeted liposomal formulations, against NB.

摘要

神经母细胞瘤(NB)是儿童期最常见的颅外实体瘤,也是婴儿期最常被诊断出的肿瘤。尽管采取了积极的治疗策略,但转移性疾病的5年生存率仍低于60%,因此,需要新的治疗方法。为了提高抗癌药物的治疗指数,同时减少副作用,现代化疗中最有前景的策略之一是基于开发创新的药物递送系统,如脂质体。与传统药物相比,“载抗癌药”脂质体已显示出更强的靶向作用于病变区域的能力以及更高的抗肿瘤疗效。由于肿瘤块内新生血管结构存在缺陷,脂质体往往优先渗出并积聚到肿瘤间质液中。通过将肿瘤特异性抗体或其他靶向部分偶联到脂质包膜表面,这种固有的肿瘤选择性可以进一步提高。在此,我们描述了这些研究中使用的方法,以及通过使用几种封装在抗体和肽靶向脂质体制剂中的“抗癌药物”针对NB所获得的抗肿瘤结果。

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