A LIPOPHILIC DERIVATIVE OF NEOCARZINOSTATIN A Polymer Conjugation of an Antitumor Protein Antibiotic*

Abstract

A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water‐soluble polymer, [(styrene)1˜3‐(maleic acid4˜7/anhydride1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential aming (of Ala‐1, ε‐amino of Lys‐20). The NCS‐polystyrene (SMANCS was a column of Sephadex G‐100 in 0.05 M ammonium bic and the main product was obtained as a single peak. The elemental and showed an increased C and a decreased N content. U.v. and i.r. absorption ectra for SMANCS showed the presence of styrene. SDS‐acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular high of about 25 000, Indicating the numbers of polymers conjugated to be six units, two of which were found attached to the two amino groups. SMANCS was solution in organic solvents, in contrast to NCS, and in water. SMANCS increased chemical and biological stability and appeared molicular in vitro biological activity.

Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

“…26,27 Furthermore, the safety of SMA has been shown in humans, as it has been approved for use in the clinic, conjugated to neocarzinostatin, as a treatment for hepatocellular carcinoma. 28,29 Lastly, using SMA to form micelles has multiple advantages over other nanoformulations. These benefits include a simple and economical preparation, high recovery, and the ability to control not only the quantity of drug encapsulated but also its release rate.…”

Passive targeting of nanoparticles to cancer: A comprehensive review of the literature

“…The tumor concentration of blue albumin mounted to ~10-fold that in the blood at 145 h. This phenomenon was also demonstrated with radio-labeled plasma proteins, including transferrin (90 kDa) and IgG (160 kDa), whereas smaller proteins, such as neocarzinostatin (12 kDa) and ovomucoid (29 kDa), did not accumulate within tumors (1,8,10). Subsequent studies have confirmed that macromolecules with a molecular weight above the renal threshold (40 kDa) tend to accumulate preferentially in neoplastic tissues upon intravenous administration (1,11).…”

The Styrene-Maleic Acid Copolymer: A Versatile Tool in Membrane Research

“…SMA copolymers also have a long-standing history in life sciences, originally being described as conjugates for drugs in cancer therapy (Maeda et al 1979;Maeda 2001). Later, it was found that SMA can interact with phospholipids to form discoidal structures that can incorporate hydrophobic molecules and therefore would be useful as a drug delivery system ( 2001).…”