Nanodesigning of multifunctional quantum dots and nanoparticles for the treatment of fibrosarcoma.

An effective, dual drug(DD) loaded nanocarrier system (nano particle(NP), quantum dots(QDs)) having two active substances was aimed to develop for the treatment of fibrosarcoma. Zinc oxide(ZnO) QDs were produced using zinc acetate dehydrate as a precursor, were incorporated with chitosan(Ch), and finally decorated with PEG-linked folic acid and were found to be effective after imatinib mesylate(IM) and dexketoprofen trometamol(DT) were loaded. Characterisations, in vitro drug releases, cell toxicities, penetrations through cell lines and in-vivo animal tests of the prepared nanosystems were performed. The size of hybrid nanoparticles were 168.6 ± 48.8 nm, surface charge was -35.8 ± 0.26 mV. The encapsulation efficiency was 75% for IM and 99% for DT. DD-functionalised QDChNPs and lyophilised functionalised QDChNPs in capsules slowed down tumour growth by up to 76.5 and 88.7%. Our results demonstrate that developed hybrid nanoparticles are highly effective. This hybrid system gathers many of the advantages of nanotechnology into one form.

Novel Approach to the Treatment of Diabetes: Embryonic Stem Cell and Insulin-Loaded Liposomes and Nanocochleates.

This study aims to investigate and compare the effects of insulin and embryonic stem-cell (ESC) loaded liposomes (LPs) and nanocochleate formulations and their PEGylated forms on the glucose levels. All formulations were characterized considering particle size, zeta potential, polydispersity index and encapsulation efficiencies. In-vitro insulin that releases from the formulations was determined using Franz-type diffusion cells. A cytotoxicity test revealed that none of the formulations was toxic to cells in any concentrations. The effects of the formulations on diabetic cells induced with glucose and streptozotocin (STZ) were then investigated in cell culture studies. Although glucose levels were decreased by the formulations after incubation, the liposomal formulations were found to be better. In experiments that were conducted on mice, it was observed again that blood glucose levels decreased successfully when diabetic pancreatic beta TC cells were incubated with the formulations, and all formulations were found to be effective in decreasing blood glucose levels in diabetic mice. Although ESC-loaded LPs were found to be the most effective formulation, LPs and nanocochleate formulations may also be used for the repair of pancreatic cells. This proposed ESC treatment is considered to be an attractive approach and a potential source for cell replacement therapy in the treatment of diabetes.

Efficacy of targeted liposomes and nanocochleates containing imatinib plus dexketoprofen against fibrosarcoma.

The main challenges in treating cancer using chemotherapeutics are insufficient dose at the target site and the development of drug resistance, while higher doses can induce side effects by damaging nontarget tissues. Combinatorial drug therapy may overcome these limitations by permitting lower doses and more specific targeting, thereby mitigating drug resistance and nontarget side effects. Recent reports indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer potential and can be used together with conventional chemotherapeutics to improve efficacy and safety. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as model drugs to develop targeted surface-modified liposome and nanocochleate formulations for fibrosarcoma treatment. The physicochemical properties and in vitro efficacy of various formulations were evaluated by measurement of particle size distribution, polydispersity index, zeta potential, encapsulation efficiency, diffusion through Caco-2 cells, and toxicity in culture. Selected formulations were then evaluated in fibrosarcoma-bearing model mice by histopathological observations and tyrosine kinase receptor inhibition assays. The most effective formulation on the fibrosarcoma model was a PEGylated nanocochleate formulation. These findings provide a foundation for developing more effective formulations and chemotherapeutic strategies for the treatment of fibrosarcoma and other types of cancer.

Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells.

Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100 nm and exhibited sustained release of pemetrexed up to 10 h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma.

Synthesis, in-vitro cytotoxic activity and DNA interactions of new dicarboxylatoplatinum(II) complexes with 2-hydroxymethylbenzimidazole as carrier ligands.

OBJECTIVES: The aim of this study was to investigate the in-vitro cytotoxic activity of new platinum(II) complexes on the human HeLa (ER-), MCF-7 (ER+) and MDA-MB 231 (ER-) cell lines. Furthermore, we investigated plasmid DNA interactions and inhibition of BamHI and HindIII restriction enzyme activity of the complex 1-4,7. METHODS: Platinum(II) complexes were synthesised from precursor complexes of [PtL2 Cl2 ] and [PtL2 I2 ]. Their cytotoxic activity was tested by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Their plasmid DNA interactions and restriction enzyme activities were also investigated using the agarose gel electrophoresis method. KEY FINDINGS: The growth inhibitory effect results showed that the cytotoxicity of complex 2 was found to be the most active complex among the synthesised complexes. CONCLUSIONS: The MTT results showed that complex 2 was found to be cytotoxic equal to cisplatin and higher than carboplatin against the MCF-7 and MDA-MB-231 cell lines. Furthermore, the estrogen or progesterone co-treatment slightly increased the cytotoxicity of complex 2, the cisplatin and carboplatin compared with the complex 2 tested alone in 50 µm concentration. According to plasmid DNA interaction and the restriction studies, complexes 1-4,7 modified the tertiary structure of pBR322 plasmid DNA, and complexes 2-4 prevented enzyme digestion at high concentrations.