Tailor-making of protein drugs by polymer conjugation for tumor targeting: A brief review on smancs

Chemical conjugation of poly(styrene-co-maleic acid) to an antitumor protein (neocarzinostatin) yielded an entirely new derivative designated as smancs (polystyrene-maleic acid conjugated neocarzinostatin). The purpose of the modification was to improve its pharmacological properties; the resulting conjugate exhibited much higher tumoritropism and lymphotropism, enhancedin vivo stability (about ten times), higher chemotherapeutic index (lower toxicity), and decreased antigenicity. Another advantage associated with this molecular engineering was an increased hydrophobicity. By this character it was solubilized in lipid contrast medium Lipiodol^R, which facilitated highly sensitive detection under x-ray-accompanying selective anticancer effectin situ. Three factors were responsible for such improvements: molecular size, hydrophobicity, and polyanionic nature. Most of the known drugs so far used as therapeutic agents are less than 1000 daltons, and those with larger molecular weights have been explored much less extensively. By polymer conjugation, the size of the drug can be extended to about 15,000 daltons (macromolecular therapeutics). The most outstanding characteristic of smancs (16,000 daltons) was the tumoritropicity, which may be a result of the highly developed neovasculature of solid tumors. Smancs as a prototype drug thus appears to lead the way in cancer drug targeting.