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Research
POLYMER MODIFIED NANOPARTICLES FOR TARGETED IMAGING AND TREATMENT OF CANCER
Recently there has been an increasing focus on the development of multifunctional nanomedicines for improvement in the remedial results of drug treatment for cancer patients. Ideally, these nanomedicines should incorporate diagnostic imaging capabilities, targeting through biomolecular recognition, and a therapeutic agent for treatment of the cancer. The surface modification of nanoparticles with well-defined polymers offers one of the most versatile methods to incorporate all of the desired components into multifunctional platforms for nanomedicines. Gold nanorods have been widely studied due to their tunable optical properties. Alteration of their shape and size has proven a useful tool to preferentially kill cancer cells through near-infrared (NIR) lasers and modification with PEG polymers has increased their biocompatibility. Though recent advances have been made in the synthesis and modification of metal nanoparticles, such as gold nanorods, the modification and characterization of metal-oxide frameworks, such as gadolinium oxide, is still limited. Gadolinium oxide nanoparticles have proven to be interesting because of their effectiveness as magnetic-resonance imaging (MRI) contrast agents. However, concerns have arisen with current in vivo use of gadolinium due to non-specific cellular uptake and accumulation within healthy cells. Modification of these particles with polymers shows promise as a means to compatiblize the surface of gadolinium nanoparticles for in vivo imaging and to affix moieties that will potentially allow for targeting and treatment of cancer cells.
RAFT polymerization was used to synthesize three different copolymers of poly (N-isopropyl acrylamide) (PNIPAM), poly (dimethylaminoethyl acrylate) (PDMAEA), and poly (poly(ethylene gycol) methyl ether acrylate) (P(PEG)MEA) with incorporation of the comonomers fluorescein O-methacrylate (FMA) at 0.45% wt and N -acryloxysuccinimide (NAOS) at 10%, 17%, and 25% wt (see below). Addition of FMA allowed for fluorescent tagging of polymer for use as an imaging moiety in fluorescence microscopy. NAOS was added as a means of attaching targeting and/or therapeutic agents. For example, the PNIPAM-co-PNAOS(25%wt)-co-PFMA was modified by the addition of folic acid (FA) through a condensation reaction with the NAOS functionality and a readily accessible primary amine of FA.
Gold nanorods were synthesized via a three-step seed-mediated approach, providing a good concentration of nanorods with an average length of 300 nm and average diameter of 25 nm. AuNRs were modified using the PNIPAM-co-PNAOS-co-PFMA copolymer synthesized via RAFT polymerization, where the trithiocarbonate end groups are available for immobilization of chains onto AuNR surfaces. TEM images confirm the formation of a relatively uniform film around the entirety of the AuNR with an average thickness of 6 nm. In combination with TEM, UV-Vis was employed to characterize the virgin nanoparticles. The AuNRs showed two main absorption maxima, the first at ~525 nm and is attributed to the transverse surface plasmon resonance absorption band. The second at a higher wavelength characteristic of the longitudinal surface plasmon band. UV-vis verifies immobilization with a comparative shift in the absorption maxima of the transverse surface plasmon from 520 nm to 527nm. amine of FA.
Gadolinium nanoplatelets were synthesized utilizing a microemulsion system, providing metal-organic platelet like nanoshapes. GdNPs were modified using the PDMAEA-co-PNAOS(25%wt)-co-PFMA copolymer synthesized via RAFT polymerization. It was determined that the addition of hexyl amine as a reducing agent was needed to provide thiol end group, which facilitated better attachment to the GdNP surface. TEM images confirmed GdNPs were successfully modified with a thin film of the PDMAEA copolymer. ATR-FTIR spectra were collected on virgin GdNPs, PDMAEA-b-PNAOS-b-PFMA copolymer, and PDMAEA copolymer grafted onto GdNPs. The virgin GdNP spectrum is fairly featureless, except the two strong peaks at 1380 cm -1 and 1520 cm -1 attributed to 1,4-BDC methylammonium ligand. Grafting of the PDMAEA copolymer onto GdNPs was confirmed by the appearance of peaks at 1650 cm -1, 2800 cm -1, 2850 cm -1, and 2950 cm -1 comparable to those characteristic of the polymer.
Further work is currently being conducted on the modification and imaging of these polymer modified nanoparticles.