polymeric nanoparticle-conjugated camptothecin DAN-222

A polymeric nanoparticle formulation of the topoisomerase I inhibitor camptothecin (CPT), an alkaloid isolated from the Chinese tree Camptotheca acuminata, covalently conjugated, via a linker, to a biocompatible polymer scaffold, with potential antineoplastic activity. Upon intravenous administration of polymeric nanoparticle-conjugated CPT DAN-222, the nanoparticles accumulate in tumor tissue and CPT is released from the formulation at the tumor site and taken up by tumor cells. During the S phase of the cell cycle, CPT selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. Compared to CPT alone, the nanoparticle formulation has a prolonged half-life and greatly improves the biodistribution of CPT resulting in an accumulation of CPT at the tumor site, which enhances tumor exposure while greatly reducing toxic side effects.