Development of multifunctional nanoparticles for drug delivery and bioimaging

Abstract

The rapid development of nanotechnology has offered novel therapeutic and diagnostic strategies to overcome limitations of conventional therapy. Creation of the materials at nanometer scale and manipulation of their properties have enabled to employ them in a number of biological applications such as in controlled drug delivery and bioimaging. Within this thesis, the physical parameters for construction of multifunctional nanoparticles were summarized and the application potential of polymeric nanoparticles and liposomes as a drug carrier and imaging vehicle were evaluated. Initially, amphiphilic hyperbranched copolymer as a drug nanocarrier was designed with dual peptides which can specifically bind to integrin αvβ3 with RGD, while Cys-TAT facilitates penetration through the cell membrane. After drug (doxorubicin (DOX)) encapsulation with detailed characterization, the applicability of the polymeric micelles was tested in glioblastoma and breast cancer cell lines that are αvβ3 integrin positive and negative, respectively. Thus, the effects of targeting ligand on the surface of nanoparticle were analyzed in terms of cellular uptake as well as toxicity. Targeted drug-loaded micelles showed stronger inhibition on the integrin αvβ3 receptor overexpressed cells compared to the drug-loaded micelles without peptides on the surface. Finally, liposome-nanoparticle hybrids were designed for co-delivery of imaging and therapeutic agents. Both hydrophobic nanoparticle (quantum dot (QD)) and hydrophilic drug (topotecan (TPT)) were encapsulated into liposomes and their further characterization was performed in detail. Drug release profile was observed under neutral and acidic conditions. In vitro analysis of the formulations was performed on cervical cancer cells. As a result, even though no targeting ligand was used on liposome surface, liposomal formulations were uptaken to the cells more efficiently compared to the free drug. Thus, the bioavailability of the imaging agent and therapeutic efficiency of the drug were enhanced by using theranostic liposome-QD hybrids. Overall, novel multifunctional polymeric and liposomal tools for drug delivery and bioimaging were designed and developed with different targeting strategies. These approaches might offer new possibilities for development of novel platforms in nanomedicine.