Adsorption/Desorption Characteristics of cis-Platin on Mercapto-Silylated Silica Surfaces Sharon Fireman-Shoresh, † Nicola Hu ¨ sing, ‡ and David Avnir* ,† Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel, and Institute of Inorganic Chemistry, The Technical University of Vienna, A-1060 Vienna, Austria Received April 5, 2001. In Final Form: June 18, 2001 High-dose cancer treatment with cis-platin (CP, cis-[Pt(NH3)2Cl2]), although of therapeutic value, is limited by its toxicity. Fast removal of excess drug shortly after administration and site-specific drug release are potential partial solutions of this problem. As a first stage toward these solutions, several adsorption/desorption properties of CP have been determined and analyzed. The main adsorbent selected for thisstudy wassilica silylated with (3-mercaptopropyl)trimethoxysilane (MPTS). The properties of this mercapto-derivatized silica (SiSH) were compared with an organically modified silica sol-gel material (Ormosil) using MPTS as modifier and withnonderivatized silica (SiOH). Although Langmuirian at first glance, a more detailed analysis of the adsorption isotherm of the CP/SiSH system revealed a cooperative mechanism of adsorption, namely, an increase in adsorption affinity with coverage. This cooperativity was detected by employing a coverage-dependent adsorption-equilibrium constant. Active shifting of the adsorption equilibrium toward the desorption side was achieved with 2,3-dimercapto-1-propane sulfonic acid sodium salt in solution. On the basis of the differences in adsorption affinities between SiSH and SiOH, we demonstrated, we believe for the firsttime, the ability to achieve interparticle migration of an adsorbate (CP)from one matrix to another. 1. Introduction cis-Platin (CP, cis-[Pt(NH 3 ) 2 Cl 2 ]) is a widely used antitumor agent which is applied in the treatment of a broad range of cancers and lymphomas. 1 A major disad- vantage of CP is its nephrotoxicity, which forces dose limitation. As a consequence, the use of high, efficient doses of this drug is less common than desired. There are several approaches to the general problem of dose limita- tion, two of which are fast removal of theexcess drug shortly after administration and the specific release of the drug atthe site of choice. More specifically, for CP, the first of these solutions would mean, for instance, to develop a highly specific extracorporeal drug adsorbent which will be part of a closed circuit: Through a vein leading to the tumor area, a high dose of CP is infused, theexcess of which is led back through another vein to theextracor- poreal CP adsorbent. 2 And the second approach would mean implanting a CP-release device near the tumor, limiting the high-dose to a localized organ. For the first approach, the adsorbent should be able to trap CP efficiently from the blood, and for the second application the adsorptive interactions between the releasing material and CP should not compete with the biochemical target of the drug. In this report we describe some first steps toward the development of such adsorbents and their characteriza- tion. These steps comprise of the preparation of suitable adsorbents and of a study of their CP adsorptive and release properties under in-vitro conditions. We were led in our choice of adsorbents by a key question of this field which arises from basic coordination-chemistry consid- erations: “Why Pt antitumor compounds do not end up bound at S-donor ligands?” 3 The question refers to a seemingly conflicting situation: While on one hand it is generally accepted thatthe final target of CP is a pair of guanine N-donors in the DNA, 4 the much more kinetically favored interaction with S-donors, plenty of which await the administrated CP on its way to the tumor, do not block the drug totally but allow some of itto reach its N-target. The currently proposed mechanism 3,4 to explain it is that while the binding of CP to S-donor ligands is indeed kinetically preferred, the two neighboringguanine residues in DNA are characterized by a specific spatial arrangement which provides a thermodynamic sink of Pt ligands. This led Reedijk 3 to propose that administrating the drug with protecting sulfur ligands can control the toxicity of CP. In view of this accumulated knowledge, it seemed to us reasonable to select S-ligand adsorbents for entrapment of CP aimed eventually both for an extracorporeal device and for a local releasing matrix. Having also in mind the eventual cost of such treatments, we selected various silicas (commercially available and sol-gel synthesized) and the commonly available thiol introducing agent, 3-(mercaptopropyl)trimethoxysilane (MPTS). Thiol-modi- fied surfaces 5 are well-known metalion extractors, 6 but to the best of our knowledge, these have not been applied for Pt 2+ adsorption. Also of relevance to this report are the preparations of various modified sol-gel materials * E-mail: david@chem.ch.huji.ac.il. † The Hebrew University of Jerusalem. ‡ The Technical University of Vienna. (1) Balmer, C.;Valley, A. W. Pharmacotherapy; Chaper 114. Calvert, H.; Judson, I.;Van der Vijgh, W. J. F. 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S.; Simoni, J. A.;Airoldi, C. Thermochim. Acta. 2000, 348, 25. 5958 Langmuir 2001, 17, 5958-5963 10.1021/la010513z CCC: $20.00 © 2001 American ChemicalSociety Published on Web 08/24/2001