Polymeric nanoparticles and cancer: Lessons learnt from CRLX101

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

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Citations (Scopus)


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.

Original languageEnglish
Title of host publicationPrivileged Scaffolds in Medicinal Chemistry
Subtitle of host publicationDesign, Synthesis, Evaluation
EditorsMartin Braddock, David Thurston
PublisherRoyal Society of Chemistry
Number of pages34
Publication statusPublished - 2016

Publication series

NameRSC Drug Discovery Series
ISSN (Print)2041-3203
ISSN (Electronic)2041-3211

ASJC Scopus subject areas

  • Drug Discovery


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