Northwestern University Robert R. McCormick School of Engineering and Applied Science

Phillip B. Messersmith Research Group

Nanomedicine

Abstract

A novel biomimetic strategy was employed for presenting antibodies on gold nanorods (NRs) to target growth factor receptors on cancer cells for use in photothermal therapy. Polydopamine (PD) was polymerized onto gold NRs, and epidermal growth factor receptor antibodies (anti-EGFR) were immobilized onto the layer. Cell-binding affinity and light activated cell death of cancer cells incubated with anti-EGFR-PD-NRs were quantified by optical imaging. PD was deposited onto gold NRs, and antibodies were bound to PD-coated NRs. Anti-EGFR-PD-NRs were stable in media, and specifically bound to EGFR-overexpressing cells. Illumination of cells targeted with anti-EGFR-PD-NRs enhanced cell death compared to non-irradiated controls and cells treated with antibody-free NRs. PD facilitates the surface functionalization of gold NRs with biomolecules, allowing cell targeting and photothermal killing of cancer cells. PD can potentially coat a large variety of nanoparticles with targeting ligands as a strategy for biofunctionalization of diagnostic and therapeutic nanoparticles.

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Abstract

Illumination of noble metal nanoparticles at the plasmon resonance causes substantial heat generation, and the transient and highly localized temperature increases that result from this energy conversion can be exploited for photothermal therapy by plasmonically heating gold nanorods (NRs) bound to cell surfaces. Here, we report the first use of plasmonic heating to locally release silver from gold core/silver shell (Au@Ag) NRs targeted to bacterial cell walls. A novel biomimetic method of preparing Au@Ag core-shell NRs was employed, involving deposition of a thin organic polydopamine (PD) primer onto Au NR surfaces, followed by spontaneous electroless silver metallization, and conjugation of antibacterial antibodies and passivating polymers for targeting to gram-negative and gram-positive bacteria. Dramatic cytotoxicity of S. epidermidis and E. coli cells targeted with Au@Ag NRs was observed upon exposure to light as a result of the combined antibacterial effects of plasmonic heating and silver release. The antibacterial effect was much greater than with either plasmonic heating or silver alone, implying a strong therapeutic synergy between cell-targeted plasmonic heating and the associated silver release upon irradiation. Our findings suggest a potential antibacterial use of Au@Ag NRs when coupled with light irradiation, which was not previously described.

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