Hydrophilic Polyhedral Oligomeric Silsesquioxane, POSS(OH)32, as a Complexing Nanocarrier for Doxorubicin and Daunorubicin

Abstract

A novel strategy, recently developed by us, to use polyhedral oligomeric silsesquioxanes (POSS) as an anti-cancer drug carrier is presented. Anthracycline:POSS complexes were prepared by simple co-addition of doxorubicin (DOX) or daunorubicin (DAU) with hydrophilic POSS(OH)32. Co-delivery of POSS and anthracyclines led to higher anti-cancer activity towards HeLa (cervical cancer endothelial) and MCF-7 (human breast adenocarcinoma) cell lines. The obtained supramolecular hybrid complexes were characterised by nuclear magnetic resonance (NMR) spectroscopy (nuclear Overhauser effect spectroscopy [NOESY] and homonuclear correlation spectroscopy [COSY]), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The two-dimensional (2D) NOESY spectra of the complexes showed the cross-correlation peaks for hydroxyl groups of POSS (~4.3–4.8 ppm) with OH groups of DOX and DAU. FTIR showed that hydroxyl group of POSS can interact with amine and hydroxyl groups of DOX and DAU. The viability of HeLa and MCF-7 was analysed with the MTT assay to evaluate the cytotoxicity of free DOX and DAU and the relevant complexes with POSS at different molar ratios. At a low DOX concentration (2.5 µM), for molar ratios 1:1, 1:4, and 1:8 (POSS:DOX), the complexes showed two and three times higher cytotoxicity towards HeLa and MCF-7 cells, respectively, than DOX itself after both 24- and 48-h incubation. The 1 µM concentration for a 1:4 POSS:DOX molecular ratio and the 2.5 µM concentration for all complexes were more toxic towards MCF-7 cells than free DOX after 48-h incubation. In the case of POSS:DAU complexes, there was higher toxicity than that of free drug after 48-h incubation. It can be concluded that the formation of non-covalent complexes increases toxicity of anthracycline drugs towards Hela and MCF-7 cells. The novel complexes are inexpensive to prepare and more effective than free drugs at low systemic toxicity.

Novel Polyhedral Silsesquioxanes [POSS(OH)32] as Anthracycline Nanocarriers—Potential Anticancer Prodrugs

“…Non-covalent systems involving anthracyclines are known to be formed and are cleaved easier than relevant conjugates [ 1 ]. The hydrogen bonded anthracyclines and POSS(OH) 32 complexes have been recently described [ 17 ]. Additionally, Figure S6 shows the graphs of absorbance intensity measured with UV-Vis for drug release from the relevant conjugates after 21 h and 42 h. It is evident that the drug release rate from conjugates is slow enough to make them potentially good candidates for anti-cancer therapy [ 17 ].…”

“…Hydroxyl functionalized silsesquioxane cage POSS(OH) 32 was synthesized according to the method described previously in the literature [ 19 ]. The reproducibility of synthesized structures was proven by three independent experiments [ 17 ]. Syntheses of succinic anhydride-modified daunorubicin (SAMDAU) and succinic anhydride-modified doxorubicin were performed according to the methods described in the literature [ 16 ] ( Figure S1 ).…”

“…The hydrogen bonded anthracyclines and POSS(OH) 32 complexes have been recently described [17]. Additionally, Figure S6 shows the graphs of absorbance intensity measured with UV-Vis for drug release from the relevant conjugates after 21 h and 42 h. It is evident that the drug release rate from conjugates is slow enough to make them potentially good candidates for anti-cancer therapy [17]. 517.54% 37.02% 47.4% PossDoxPEGB3 616.38% 27.00% 60.7% PossDauPEG1 742.33% 54.50% 77.7% PossDauPEG2 819.20% 33.93% 56.6% PossDauPEGB3 919.52% 27.18% 71.8%…”

“…The hydrogen bonded anthracyclines and POSS(OH)32 complexes have been recently described [17]. Additionally, Figure S6 shows the graphs of absorbance intensity measured with UV-Vis for drug release from the relevant conjugates after 21 h and 42 h. It is evident that the drug release rate from conjugates is slow enough to make them potentially good candidates for anticancer therapy [17]. As the plots in Figure 4 prove, the conjugates (4 and 7) containing PEG1 in their structure show the slowest rate release of the drugs, while the PEG2-containing conjugates show higher and similar release profiles.…”

Is acriflavine an efficient co-drug in chemotherapy?

“…Based on our previous publications, the interaction of doxorubicin with the carriers can be studied by NMR spectroscopy. [44][45][46][47] NMR can determine which protons are involved in the interaction of ACF with DOX and help determine the type of interaction. To determine the involvement of protons of the hydroxyl groups, the 1 H NMR spectra of the pure doxorubicin solution and the doxorubicin-acriavine mixture solution (Fig.…”