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Chapter 8

Polymeric Nanoparticles and Cancer: Lessons Learnt from CRLX101

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-1α (HIF-1α) 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-1α and cancer stem cells. Moreover, we discuss the therapeutic value of combining HIF-1α inhibition with antiangiogenics. Finally, we return to CRLX101 and cover in detail the latest preclinical and clinical evaluations and discuss future directions.

Publication details

Print publication date
28 Apr 2016
Copyright year
Print ISBN
ePub eISBN
From the book series:
Drug Discovery