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2 2013

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Mechanizm oporności na leki platynowe oraz strategie pokonywania tego zjawiska

Weiss-Gradzińska W., Krzempek W., Trynda-Lemiesz L.

Wiadomości Chemiczne

2013

[Z] 67, 11-12

1105--1128

Platinum drugs belong to one of the oldest [2] and best investigated groups of cytotoxic drugs. On account of their high efficacy and alkylating-like action [14] they are used in a treatment of various types of neoplasms [3–5]. Despite investigators’ best efforts survival time of patients diagnosed with cancer is still short. Responsible for the fact is high toxicity of used therapeutic methods and development of resistance to them [3–5, 19]. In this paper authors review reasons behind decreased sensitivity of neoplastic cells to platinum treatment and discuss the newest promising trends in its overcoming. Due to different properties of neoplastic cells, availability of a chemotherapeutic agent inside a tumour is limited [9–12]. Moreover continuous development of resistance to platinum drugs further decreases their cellular concentration and inactivates their functions. Also owing to increased activity of DNA repair systems, higher tolerance to genome deformations and numerous mechanisms that lead to impaired apoptosis, drug efficacy is reduced [3-5, 19]. In order to increase a potency of platinum agents new therapeutic strategies are investigated. Coadministration with resistance modulators [20, 22, 23] and combination therapy with other antineoplastic drugs [8, 24–30] have already proved their effectiveness. Additionally, newer generations of platinum drugs are developed [15–18]. Mostly platinum(IV) prodrug complexes often releasing axial ligands with their own pharmacological action [5, 6, 31], but also multi-nuclear platinum compounds that form more complex DNA-adducts [32–35]. Other strategies include the development of innovative dosage forms such as single walled carbon nanotubes (SWCNTs), multiwalled carbon nanotubes (MWCNTs) [38, 39] or encapsulation [36, 37]. Finally utilisation of oncolytic viruses could be a way to selectively destroy neoplastically transformed cells [40].

Badanie cytotoksyczności nowych nośników leków platynowych

Werengowska-Ciećwierz K, Wiśniewski M., Terzyk A. P., Bielicka A., Gurtowska N., Drewa T. A.

Inżynieria i Ochrona Środowiska

2013

T. 16, nr 2

263--271

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.