当前位置: X-MOL 学术J. Control. Release › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Towards clinical translation of ligand-functionalized liposomes in targeted cancer therapy: Challenges and opportunities
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2018-03-01 , DOI: 10.1016/j.jconrel.2018.02.040
Lisa Belfiore , Darren N. Saunders , Marie Ranson , Kristofer J. Thurecht , Gert Storm , Kara L. Vine

The development of therapeutic resistance to targeted anticancer therapies remains a significant clinical problem, with intratumoral heterogeneity playing a key role. In this context, improving the therapeutic outcome through simultaneous targeting of multiple tumor cell subtypes within a heterogeneous tumor is a promising approach. Liposomes have emerged as useful drug carriers that can reduce systemic toxicity and increase drug delivery to the tumor site. While clinically used liposomal drug formulations show marked therapeutic advantages over free drug formulations, ligand-functionalized liposomes that can target multiple tumor cell subtypes may further improve the therapeutic efficacy by facilitating drug delivery to a broader population of tumor cells making up the heterogeneous tumor tissue. Ligand-directed liposomes enable the so-called active targeting of cell receptors via surface-attached ligands that direct drug uptake into tumor cells or tumor-associated stromal cells, and so can increase the selectivity of drug delivery. Despite promising preclinical results demonstrating improved targeting and anti-tumor effects of ligand-directed liposomes, there has been limited translation of this approach to the clinic. Key challenges for translation include the lack of established methods to scale up production and comprehensively characterize ligand-functionalized liposome formulations, as well as the inadequate recapitulation of in vivo tumors in the preclinical models currently used to evaluate their performance. Herein, we discuss the utility of recent ligand-directed liposome approaches, with a focus on dual-ligand liposomes, for the treatment of solid tumors and examine the drawbacks limiting their progression to clinical adoption.



中文翻译:

靶向靶向治疗中配体功能化脂质体的临床翻译:挑战与机遇

对靶向抗癌疗法的治疗耐药性的发展仍然是一个重要的临床问题,肿瘤内异质性起着关键作用。在这种情况下,通过同时靶向异质性肿瘤内的多种肿瘤细胞亚型来改善治疗效果是一种有前途的方法。脂质体已经成为有用的药物载体,可以降低全身毒性并增加药物向肿瘤部位的递送。尽管临床上使用的脂质体药物制剂相对于游离药物制剂显示出显着的治疗优势,但可靶向多种肿瘤细胞亚型的配体官能化脂质体可通过促进药物递送至组成异质性肿瘤组织的更广泛肿瘤细胞群体而进一步提高治疗功效。通过表面附着的配体将药物吸收引入肿瘤细胞或与肿瘤相关的基质细胞,因此可以提高药物递送的选择性。尽管有希望的临床前结果表明配体导向脂质体的靶向性和抗肿瘤作用得到改善,但这种方法在临床上的翻译仍然有限。翻译面临的主要挑战包括缺乏扩大规模生产和全面表征配体功能化脂质体制剂的既定方法,以及体内重现能力不足目前在临床前模型中评估肿瘤的表现。本文中,我们讨论了针对配体脂质体的新型配体定向脂质体方法在治疗实体瘤中的实用性,并探讨了限制其发展为临床应用的弊端。

更新日期:2018-03-01
down
wechat
bug