|TOPO-1 and HIF-1alpah [ref.1]|
|CRLX101 is a novel approach to cancer chemotherapy that is under investigation in human trials. It is an example of a nanomedicine. The agent represents a nanoparticle conjugate that consists of a drug delivery molecule, namely a cyclodextrin-based polymer (CDP) and an anti-cancer compound (camptothecin).
Camptothecin (CPT), an alkaloid extract with poor water solubility from plants such as camptotheca acuminata, exhibits anti-cancer activity possibly due, at least in part, by the inhibition of DNA topoisomerase I resulting in cell death. In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta-cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water-soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolysed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect and as a result, the anticancer drug is enhanced and retained in the tumor tissue.