One of the promising avenues for delivery of poorly water soluble chemotherapeutics in increased effective concentration is through the use of nanoparticles. The use of nanovectors has been a promising avenue due to their inherent versatility, increased multivalency and ability to passively target tumors through the enhanced permeability and retention (EPR) effect. Within the diverse field of nanovectors, dendrons and dendrimers (synthetic macromolecular polymers with tightly controlled geometry and structure) have shown impressive potential for targetted delivery of therapeutics.<br/><br/>This project is aimed towards the preparation of 30 nm dendron-carrying gold nanovectors with various terminal functional groups (amine, carboxylate, and hydroxyl) for their use in drug delivery and in vivo imaging. The aforementioned nanovectors have been designed with three complimentary components. (i) A 20 nm gold core (ii) Dendrons carrying imaging agents such as: (DOTA chelated Gd) for MRI and water-soluble Cy 7 dye for fluorescence Imaging. (iii) Dendron carrying tumor recognition moieties (e.g. carrying monoclonal antibodies) for active targeting. In the present research, gold nanoparticles have been utilized as a non-classical dendrimer core due to its well-established biocompatibility and its dimension has been carefully selected to minimize rapid clearance via renal filtration or elimination via macrophages due to opsonization. For this project, poly(propyleneimine) dendrons were prepared with various terminal functionalitites. Additionally, a TEG (Tetra Ethylene Glycol) spacer was incorporated at the focal point of the dendron to minimize steric repulsion between the brances while increasing its biocompatiblity . The cytotoxicity and cellular fate of the thus prepared dendronized gold nanoparticles was studied in MCF-7 breast cancer cell lines using fluorescence microscopy.<br/><br/>It is important for any drug delivery scaffold to maintain the integrity of cellular membranes without exhibiting inherent cytotoxicity. To elucidate the cellular fate of the nanocarrier, chlorin-carrying dendrons were utilized to visualize the nanoparticle compartmentalization within cellular organelles. Furthermore, the integrity of the cellular membrane was studied as a function of the surface charge of nanoparticle coatings. From these studies, an optimum scaffold was identified for the creation of theranostics which will be tested for efficacy of drug delivery against PC3 cancer cell.

Study of cellular localization and toxicity of dendronized gold nanoparticles for theranostic applications

254th National Meeting (2017)

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