Macromolecular anticancer agent, PEGylated Zinc protoporphyrin (ZnP) targeting HSP32

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We prepared two types of polymeric drugs having anti-HO-1 and antitumor activities, (i) PEGylated ZnPP (covalently linked ) and (ii) SMA-ZnPP micelles. Cell uptake was several fold faster in SMA-ZnPP micelles than PEG-ZnPP conjugates. They exhibited both in vitro cytotoxicity and in vivo antitumor activity having IC_<50> of 1-7μM and 10mg/kg in vivo respectively. They also exhibited enhanced cytotoxicity to human tumor cells (CML cell line, K562 ; ATL cell line, MT-2 ; esophageal cell line, Kyse 510) in culture under the exposure to LED light at 420nm. Mouse tumors were more effectively suppressed with SMA-ZnPP plus LED light at 420nm than drug alone both in vivo and in vitro. PEG-ZnPP conjugates (covalent) undergo hydrolytic cleavage by serine and thiol proteases in the tumor tissue and released free ZnPP, whereas SMA-ZnPP micelles underwent micelle disintegration upon the contact with to cell membrane components such as lecithin, and released the drug ZnPP effectively in cells.