Polymeric Nanoparticles and Cancer: Lessons Learnt from CRLX101

CRLX101 (formerly IT-101) is a novel cyclodextrin-based polymer that selfassembles into nanoparticles. CRLX101 was designed to deliver sustained levels of the cytotoxic agent camptothecin (CPT) to tumour cells while minimizing delivery to normal tissue. Covalent conjugation of hydrophobic CPT to the cyclodextrin polymer increases its water solubility by three orders of magnitude and prevents inactivation through spontaneous lactone ring opening, a process that occurs rapidly at physiologic pH. CPT derivatives such as irinotecan (CPT-11, Camptosar; Pfizer) and topotecan (TPT, Hycamtin; GlaxoSmithKline) demonstrate clinical utility for the treatment of advanced solid tumours. The primary cellular target of