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A long-circulating co-polymer in "passive targeting" to solid tumors.

A Bogdanov·S C Wright·E M Marecos·A Bogdanova·C Martin·P Petherick·R Weissleder
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Abstract

A co-polymer of O-methyl polyethylene(glycol)-O'-succinate (MPEGs, m.w. 5100) and poly-l-lysine (PL, median m.w. 32700, degree of polymerization 256) has been synthesized by covalent grafting. The resultant MPEGs-PL (30% modification degree of epsilon-amino groups) had a hydrodynamic diameter corresponding to a 690 kD protein. Free amino groups (180/mol of the co-polymer) were used for conjugation of diethylene pentaacetic or succinic acid residues to MPEGs-PL. The potential of the resultant compound as a carrier of therapeutic and diagnostic drugs was studied using a rodent carcinoma models. The co-polymer had a blood pool half-life of 36h in adenocarcinoma-bearing rats. Radioactively labeled preparations were resistant to trans-chelation with apotransferrin and stable in blood for 24 h. The co-polymer accumulated in solid tumors at the level of 1.5-2% injected dose/g of tumor in 24 h. At that time, 34-40% of the accumulated polymer was associated with tumor cell fraction. The co-polymer non-covalently associated with cis-diamminedichloroplatinum(II), showed a cytostatic effect against mouse F9 carcinoma, and induced a reversal in tumor growth after intravenous administration.

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AnimalsDrug CarriersFemaleMiceMice, Inbred BALB CNeoplasms, ExperimentalPolyethylene GlycolsPolylysineRatsTechnetium Tc 99m PentetateTissue DistributionTumor Cells, CulturedJournal Article

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A Bogdanov, S C Wright, E M Marecos, A Bogdanova, C Martin, P Petherick, R Weissleder. 1997. A long-circulating co-polymer in "passive targeting" to solid tumors.. https://doi.org/10.3109/10611869708995848

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