Polymeric nanoparticles and cancer: Lessons learnt from CRLX101

Ismael Gritli, Edward Garmey, Scott Eliasof, Andres Tellez, Mark E. Davis, Yen Yun

研究成果: 書貢獻/報告類型章節

4 引文 斯高帕斯(Scopus)

摘要

CRLX101 (formerly IT-101) is a novel cyclodextrin-based polymer that self-assembles into nanoparticles. CRLX101 is covalently conjugated to the hydrophobic topoisomerase 1 (TOP1)-inhibitor camptothecin (CPT) resulting in stabilized structure and increased water solubility. Extensive preclinical studies of CRLX101 demonstrated delayed renal clearance and a prolonged plasma half-life. The nanoparticle passively accumulates in tumour tissue through the enhanced permeability and retention effect and slowly releases active CPT leading to enhanced TOP1 inhibition, potential hypoxia inducible factor-1a (HIF-1a) effect, cancer stem cell targeting, and increased antitumour activity against multiple human tumour xenografts. More than 200 human cancer patients have been treated with CRLX101 in phase I/IIa and phase II clinical trials. In this chapter we explore a wide range of anti-cancer nanotherapeutic strategies to inhibit TOP1, HIF-1a and cancer stem cells. Moreover, we discuss the therapeutic value of combining HIF-1a inhibition with antiangiogenics. Finally, we return to CRLX101 and cover in detail the latest preclinical and clinical evaluations and discuss future directions.
原文英語
主出版物標題Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis, Evaluation
發行者Royal Society of Chemistry
頁面199-232
頁數34
2016-January
版本51
DOIs
出版狀態已發佈 - 2016
對外發佈

出版系列

名字RSC Drug Discovery Series
號碼51
2016-January
ISSN(列印)20413203
ISSN(電子)20413211

ASJC Scopus subject areas

  • 藥物發現

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