Chemical as pects of targeted anticancer therapy I. Covalent bond of ligand to carier

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

The Cytotoxicity Analysis of New Platin Drug Carrier

Przedstawiono zastosowanie nanorurek węglowych jako potencjalnych kontenerów leków platynowych. Nanorurki węglowe ze względu na swoje właściwości mogą z powodzeniem zostać zastosowane w nowoczesnych nośnikach leków. Budowanie nowych systemów dostarczania chemioterapeutyków na bazie nanorurek węglowych jest nowatorską metodą leczenia chorób nowotworowych. Celem pracy jest przedstawienie metod biokoniugacji cytostatyków. Chemioterapeutyk może zostać umieszczony we wnętrzu nanorurki węglowej bądź na jej zewnętrznej powierzchni. Metody wprowadzania leków obejmują oddziaływania niekowalencyjne (adsorpcję) oraz kowalencyjne tworzące grupy: estrowe, amidowe i N-acetylohydrazonu. Dodatkowo, tematyka pracy skierowana jest na analizę badań cytotoksycznych nowatorskich układów nanonośników dostarczających związki kompleksowe platyny przeciwko komórkom nowotworowym różnego typu: głowy, szyi, czerniaka, piersi czy jajników. Zastosowanie nowych nośników leków daje możliwości uzyskania satysfakcjonujących rezultatów leczenia chorób nowotworowych.The article includes the results showing application of carbon nanotubes as potential containers of platin drug. Carbon nanotubes have special properties which are very useful and suitable in the building of modern drug delivery systems. Traditional anticancer therapy is usually in effective because of a low selective action of drugs and their minimized biodistribution in organism. Moreover, this chemotherapy is associated with high risk of recurrence or unsatisfactory effectiveness and undesirable side effects. The formation of new drug delivery system based on carbon nanotubes is innovative method of anticancer treatment. This idea includes the branch of nanomedicine expanding the traditional medicine. The major purposes of nanomedicine are construction of drug delivery systems and noninvasive treatment. We described the types of drug associations to carbon nanotubes. Chemotherapeutics could be aggregated on the internal surface of nanocarriers, mainly by nanoextraction and nanocondensation process. The drugs linked with the external surface of carbon nanotubes can be linked by covalent or noncovalent bonds. The adsorption is connected with π-π interaction. In turn, the chemical bonds between the drug and the surface of carbon nanotubes can form ester, acethylhydrazone and amide groups. The types of reactions depend on the functional groups which are offered by the nanocarrier and the structure of drug. In most cases, surface of carbon nanotubes must be initially modified. This functionalization is associated with the covering with polymers as polyethylene glycol or the application of oxidation process. Additionally, the special modification of carbon nanotubes surface makes them biocompatible. The purpose of this study is to describe the analysis of cytotoxicity of new drug delivery systems based on carbon nanotubes and platin compounds. The new drugs delivery systems based on carbon nanotubes should minimize side effects and improve final results of therapy. These effects are confirmed in the literature. These cited papers proved that the application of carbon nanotubes in delivery system of platin compounds is useful during anticancer therapy and can give the positive effect in future

Chemical aspects of targeted anticancer therapy II . Bond of carrier to drug

Traditional anticancer therapy is usually low effective. Popular and common drugs applied in anticancer therapy are characterized by low solubility and nonspecific biodistribution in an organism. The chemotherapy kills not only cancer but also healthy cells [4]. Building of modern drug delivery systems based on nanocarriers is a new method of anticancer treatment. The present study is directed towards nanomaterials (as carbon nanotubes, liposomes, polymeric micelles) as modern drug carriers. Thus, we characterized mechanisms of actions of traditional chemotherapeutics: paclitaxel, cisplatin and doxorubicin (Figs. 3–5) [1, 15, 21]. The purpose of this study is a description of the bioconjugation of drug-nanocarrier. Chemotherapeutics can be connected to external or internal surfaces of nanocarriers (Fig. 6) [6]. We described two main methods of drug delivery from internal space of nanocarriers: nanoextraction and nanocondensation (Fig. 7) [32]. The type of drug-carrier bonding can be covalent or noncovalent. We report recent advances in the field showing the formation of esters (Figs. 10–11) [28, 29, 53, 54], acethylhydrazone (Fig. 12) [55–61], amides [62–64], and disulfides groups [12, 65]. These reactions depend on functional groups in structures of drugs and require suitable modification of nanocarrier surfaces. In practice, the functionalization of nanocarrier surface is associated with the covering with polymers including PE G, HPMA, PG and PL GA [3]. Adsorption is the most popular process of bonding chemotherapeutic and nanomaterials (Fig. 13) [66]. Special attention is paid to electrostatic interaction between drugs: paclitaxel [74], cisplatin [59, 76, 77], doxorubicin [67–73] and nanocarriers: carbon nanotubes and/or polymeric micells. By application of modern anticancer therapy, drugs are preserved from lysosomal degradation and to fast reaction in biological environment. Finally, nanocarriers improve adsorption of drug and increase concentration of drug only in cancer tissues [6, 7]