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Bioactive agents carrying quantum dot labeled liposomes

Büyüksungur, Arda
Among the many possible applications of nanotechnology in medicine, the use of various nanomaterials as delivery systems for pharmacologically active agents, drugs and nucleic acids (DNA, siRNA), and imaging agents is gaining increased attention. Liposomes are particularly important for these drug delivery systems because of their advantages such as their ability to carry hydrophilic and hydrophobic drugs, their being of biological origin and short life spans. Quantum Dots (QDs) are nano-scale, semiconductive, fluorophore crystals of inorganic origin. QDs are highly resistant against photobleaching unlike organic, fluorescent dyes and are very suitable for use as tracking agents. Cancer tissues produce angiogenesis agents such as VEGF, and angiopoietin that lead to the production of new blood vessels. These vessels of cancer tissue have a chaotic structure. Abnormal and dysfunctional blood vessels are a hallmark of solid tumors and they prevent medication from reaching and killing cancer cells. In the recent years, however, drug release systems were developed to use these highly porous blood vessels for cancer drug delivery. In this study liposomes were tested for their ability to attach to charged surfaces and were shown to perform this function especially on oppositely charged surfaces. Polystyrene sulfonate and poly(allylamine) were used to coated onto glass surfaces and were found successful by binding oppositely charged liposomes; cationic liposomes were attached preferably an anionic regions coated onto glass surfaces and anionic liposomes were attached preferably an cationic regions coated onto glass surfaces. Polymer brush surfaces were used to investigate the liposomal preference towards the surfaces. Cationic multilamellar liposomes and cationic extruded SUV liposomes were attached preferably on negatively charged PMA polymer brushes. Cationic extruded liposomes found to be more stable than the multilamellar liposomes on the surfaces. Doxorubicin, an anticancer drug, is used in cancer therapy due to its cytotoxic effect towards the cells. Liposomes decreased the cytotoxic effect of the doxorubicin and released doxorubicin for more extended periods. Quantum Dots with CdTe core were used as the imaging or tracking agent to observe the route of liposomes. Liposomes masked the cytotoxic effect of CdTe quantum dots arising from the inorganic core by 30%. The fluorescent quantum dots were entrapped in liposomes and observed under a confocal microscope and the interactions of the liposomes and Saos2 cells were studied. Real time observation studies showed both cationic and neutral liposomes bound to the Saos2 cells but cationic liposomes shown to be faster in binding to Saos2 cells. Bevacizumab, anti-angiogenesis agent, was tested for its ability to prevent HUVEC from proliferation was shown to be ineffective in tested conditions but it was found that the drug decreased proliferation of HITAEC.