Abstract
Anthracyclines belong to the anticancer drugs that are widely used in chemotherapy. However, due to their systemic toxicity they also exert dangerous side effects associated mainly with cardiovascular risks. The pathway that is currently often developed is their chemical and physical modification via formation of conjugated or complexed prodrug systems with a variety of nanocarriers that can selectively release the active species in cancer cells. In this study, six new nanoconjugates were synthesized with the use of polyhedral oligosilsesquioxanes [POSS(OH)32] as nanocarriers of the anticancer drugs anthracyclines—doxorubicin (DOX) and daunorubicin (DAU). These prodrug conjugates are also equipped with poly(ethylene glycol) (PEG) moieties of different structure and molecular weight. Water-soluble POSS, succinic anhydride modified (SAMDOX and SAMDAU) with carboxylic function, and PEGs (PEG1, PEG2 and PEGB3) were used for the synthesis. New nanoconjugates were formed via ester bonds and their structure was confirmed by NMR spectroscopy (1H-NMR, 13C-NMR, 1H-13C HSQC, DOSY and 1H-1H COSY), FTIR and DLS. Drug release rate was evaluated using UV-Vis spectroscopy at pH of 5.5. Release profiles of anthracyclines from conjugates 4–9 point to a range of 10 to 75% (after 42 h). Additionally, model NMR tests as well as diffusion ordered spectroscopy (DOSY) confirmed formation of the relevant prodrugs. The POSS-anthracycline conjugates exhibited prolonged active drug release time that can lead to the possibility of lowering administered doses and thus giving them high potential in chemotherapy. Drug release from conjugate 7 after 42 h was approx. 10%, 33% for conjugate 4, 47% for conjugate 5, 6, 8 and 75% for conjugate 9.
Highlights
We are currently witnessing a rapid development of anticancer drug delivery systems [1,2], exploiting such nanocarriers as, e.g., gold and mesoporous silica nanoparticles, polymers, and dendrimers [3]
Nanotechnology and nanomedicine [4,5] offer a variety of systems that are intensively studied as delivery vehicles, modulating cytotoxicity and mediating sustained drug release in tumour tissues
T8[(CH2)2S(CH2)2OH]8 applied in the model reaction has a well-defined structure, in con4 of 15 trast to [polyhedral oligosilsesquioxanes (POSS)(OH)32] being a mixture of cage silsesquioxanes
Summary
We are currently witnessing a rapid development of anticancer drug delivery systems [1,2], exploiting such nanocarriers as, e.g., gold and mesoporous silica nanoparticles, polymers, and dendrimers [3]. The curr research presents results on application of hydrophilic silsesquioxanes, known in the are well known to facilitate cell membrane penetration [12], an important feature in drug erature as [POSS(OH)32], as novel anthracycline nanocarriers, synthesized by hydroly delivery. They are biocompatible [13] and nontoxic [14]. The research was aimedglycol; to develop synthetic methods of silsesquioxane nanoconjugates with anticancer drugs Such conjugates would be capable daunorubicin and PEG1—PossDauPEG1. Develop effective synthetic methods of silsesquioxane nanoconjugates with antican drugs Such conjugates would be capable of releasing active drugs in cancer cells.
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