Preparation And In Vitro Bioactivity Investigation Of Two Pt-BSA Conjugates

Cisplatin is a broad-spectrum anti-tumor drug, but because of its negative factors such as no targeting, low solubility, large toxicity, researchers have been committed to the development of low toxicity and high effect anti-tumor platinum drugs. The prodrug of cisplatin with different carriers may increase the solubility, control the release speed, extend the cycle period in the body, increase the stability and reduce the side effects of the drug, etc. It was reported that Pt(IV) complexes are accepted as a class of potential anticancer compounds with better oral activity than their Pt(II) analogues such as cisplatin or carboplatin and represent a potential opportunity to overcome the problems associated with cisplatin:resistance, toxicity, low solubility and absorption, and poor pharmacokinetic profiles.As a result of the advantages such as it is biodegradable, biocompatible, non-toxic and non-immunogenic, albumin have attracted more and more attentions from the researchers, and which is widely used as diagnostic reagents and drug carriers. The most widely used albumin is human serum albumin(HSA) and bovine serum albumin(BSA).In our research, we mainly concerned with the following aspects:First, we prepared two prodrugs of platinum complex with the carrier of BSA:1) We prepared the CDDP-BSA conjugates(Pt(II)-BSA).2) We synthesized cis, cis,trans-[Ptâ…£C12(OH)2(NH3)2] and conjugated it with BSA.Second, the release behavior of the two conjugates was investigated in the different media mimic the in vivo environments. The results indicated that the release possess the sustained-release characteristics and depends on the pH conditions, the platinum release rate from the micelles at pH5.0was significantly faster than that at pH7.4. Specially. Pt(IV)-BSA showed a sudden release in aqueous solutions of sodium ascorbate which mimics the reductive environment inside cells.Third, the interactions of the two conjugates with DNA were performed with UV-Visible absorption spectra, viscosimetry, gel electrophoresis and so on, which revealed that there is no intercalation or partial intercalation between the conjugates and DNA. Both of the two conjugates exhibited the cleavage activity to pUC18DNA.Forth, the cytotoxicity of the CDDP-BSA and Pt(IV)-BSA were investigated using MTT method. Both of them exhibited significant inhibition of the proliferation of cancer cells.