There are currently several challenges in chemotherapy including increased efficacy, high potency and accurate targeting of the cancer cells. The multiple side effects along with increased drug resistance against traditional chemotherapeutic agents have presented ongoing challenges to the efficacy of cancer therapy. At the present time, researchers are investigating several novel drug delivery systems. One of the promising avenues among the aforementioned has been the use of nanovectors due to their inherent versatility, high multivalency and ability to passively target tumors. Among nanovectors, dendrons, nanoparticles and dendrimers (synthetic spherical polymeric molecules with tightly regulated structure/geometry) have shown great potential for therapeutic use. This project is aimed towards the preparation of a nanovector comprised of four complimentary components: (i) A nanometer sized gold core, (ii) Dendronized therapeutic agents (e.g. carrying cisplatin, docetaxel ), (iii) Dendronized Imaging agents for MRI (magnetic resonance imaging) or fluorescence imaging and (iv) Dendronized tumor recognition moieties (e.g. carrying monoclonal antibodies). In the current research, gold nanoparticles (18-20 nm) have been used as the non-traditional dendrimer core due to its inherent biocompatibility. The careful selection of this size will prevent the thus synthesized gold nanoparticles from being either quickly eliminated through renal filtration or uptaken by the host macrophages due to agglutination. For the current project, poly(propyleneimine) dendrons that have shown potential as proton sponges were prepared. Furthermore, a TEG (Tetra Ethylene Glycol) molecule was incorporated at the focal point of the dendron to allow for enhanced biocompatibility and water solubility. The functionalization of these dendrons have been performed for the creation of a library of complimentary agents such as synergistic drugs, imaging moieties and targeting ligands to be incorporated onto the gold surface. The dendron-TEG scaffold has been functionalized with Gd-DOTA (Gadolinium-1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid) to generate multifunctional gold nanoparticles as advanced contrast agents for MRI and with Indocyanine based NIR dyes (ICG) for advanced optical imaging in in vitro and in vivo conditions. The future goal of the project is the optimization of the conjugation of MRI/NIR agents and the incorporation of chemotherapeutics and targeting agents.

Synthesis of multifunctional dendronized-gold nanoparticles for bimodal in vivo imaging

253rd National Meeting (2017)

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