Chemiczne aspekty celowanej terapii przeciwnowotworowej I. Kowalencyjne połączenia ligand-nośnik

In this study we describe the most popular biomedical engineering nanoparticles including carbon nanotubes [17-20], liposomes [4-7], polymeric micells [11-13], quantum dots [3, 21-23], hydrogels [24-27], dendrimers [14-16] which are recently considered as modern drug carriers. These nanomaterials are applied for cancer diagnostic and targeted delivery of active compounds as chemotherapeutics in so called targeted therapy. Thus, we characterized the ideas of targeted therapy for which compositions of carriers with antibody are constructed (Figs. 3, 4). We also compared the traditional and targeted mechanisms [1, 3, 28-29] of drug delivery (Fig. 2). During targeted therapy only the essential dose of drug (less than during conventional chemotherapy) is delivering to the cancer cell. In additional, the application of targeted therapy reduces side effects, being very characteristic for the traditional treatment. The anticancer compound can selectively hits the target only, due to the presence of the ligands attached to the surface of nanocarirer. We characterized ligands which are often use in nanomedicine: antibodies [33-37], folic acid [30-33], peptides [33, 38, 39], aptamers [33, 40, 41] and transferrin [33, 42-44]. The purpose of this study is description of the bioconjugation of ligand-nanocarrier. This step is necessary and very important in synthesis of the novel drug delivery systems in targeted anticancer therapy. We report recent advances in the field showing the formation of amides (Figs. 6-8) [51-57], thioethers (Figs. 9-11) [52, 60-66], disulfides (Fig. 12) [69], and acethyl-hydrazone groups (Fig. 13) [73]. Special attention is paid to the process such as Diels-Alder (Figs. 14, 15) [74, 75] and "click chemistry" through the cycloaddition of Huisgen (Figs. 16, 17) [79-82]. We describe also the reaction of Staudinger [83] and the process of formation Schiff 's base [84]. The processes enable very mild and selective modification of the carriers through formation of amide bound. These methods ware less popular but allow the fictionalization of nanocarriers in biomedical application. Each reaction or process needs special and individual environment and conditions, which are summarized in Table 1.