Antitumor polymers

Since the pioneer work by Merigan in 1967 [1], many kinds of synthetic or natural polyanionic polymers have been examined for their biological activities [2-8], such as cytotoxicity, antiviral activity, antitumor activity, and immunomodulating activity. Although the biological results were interesting, the extent of activity for clinical application was still low. 

Presently there are two polyanionic polymers, MVE-2 and Carbetimer, that have undergone considerable clinical evaluation as antitumor agents. 

Veronese FM, Schiavon O, Pasut G, Mendichi R, Andersson L, Tsirk A, Ford J, Wu G, Kneller S, Davies J, Duncan R (2005) PEG-doxorubicin conjugates influence of polymer structure on drug release, in vitro cytotoxicity, biodistribution, and antitumor activity. Bioconjug Chem 16 775-784... 

We have used of water-soluble polymers, such as polysaccharides, as carriers of antitumor agents to reduce their side effects [3]. In this study,... 

Chen R, meng F, Liu Z, Chen R, Zhang M. Antitumor activities of different fractions of polysaccharide purified from Ornithogalum caudatum Ait. Carbohydrate Polymers 2010 80 845-851. 

SMANCS (Styrere-co-maleic acid/anhydride polymer bound to neocarzinostatin Neocarzinostatin (an antitumor protein) Amide bond between polymer carboxyl and protein amino None N/A SMANCS showed anticancer activity against many tumor cell lines, and had lower IC50 values than five other anticancer agents tested Liver tumors reduced more than 50% after 6 months in human subjects 15, 56, 57... 

In recent years, many fungi were examined for potent antitumor polysaccharides and a great number of different carbohydrate polymers could be isolated and shown to have a quite distinct antitumor activity. The most active ones have p-1,3- and 1,6-linkages and glucose as the main structural monomer. 

Maeda, H., L. Seymour, and Y. Miyamoto. 1992. Conjugates of antitumor agents and polymers advantages of macromoleculartherapeutibsvivo. Bioconjugate Cherr8 351-362. 

Schacht and coworkers in Belgium201-212 used pellets of a polyphosphazene with both ethyl glycinate and ethyl phenylalanate side groups for the controlled release of the antitumor agent, mitomycin-C. A 100% ethyl glycinato polymer released the drug too rapidly, but mixed-substituent polymers with 50-65% phenylalanine ester released the drug at an optimum rate. 

Some drugs can also be linked to a water-soluble polymer by coordination. The platinum complex, (NH3)2PtCl2, is a well-known antitumor agent. Because the drug is... 

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