Novel EPR-independent camptothecin conjugate with dual-phase drug release: a blood pool effect?

摘要

Most antineoplastic polymer-based drug conjugates accumulate in tumors due to the increased neovascular permeability (EPR effect). A water soluble camptothecin (CPT) conjugate having a dual phase drug release mechanism was developed that demonstrated higher antitumor efficacy and lower toxicity in xenograft models then control small molecule drugs (CPT and CPT-11). However, the delivery of CPT to the tumor tissue did not correlate with EPR effect in the same tumors. Most likely the efficacy of the conjugate is due to a "blood pool" effect: increased release of the CPT prodrug in the intratumoral blood pool and immediate "anchoring" in tumor tissues.