Targeting polydopamine-coated gold nanocages to tumor cells using the anti-angiogenic peptide anginex

by Jenkins, Samir; Dings, Ruud; Chen, Jingyi; Griffin, Robert; Nedosekin, Dmitry

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Tumor targeting is a crucial consideration when designing nanoparticle-based theranostic agents for in vivo use. The absence of targeting leads to low accumulation efficiency at the tumor site; small mol. targeting agents may lack specificity, and antibodies may not be robust enough to handle prepn. and storage. Anginex is a synthetic 33mer, which can be exploited to inhibit tumor endothelial cell proliferation, tumor angiogenesis, and tumor growth. Anginex' activity arises from binding galectin-1, which is secreted by malignant tumor cells. The goal of the present study is to demonstrate the ability to conjugate anginex to polydopamine-coated gold nanocages, and then use these targeted particles to treat triple-neg., galectin-pos. tumor cells. Photoacoustic flow cytometry was used to demonstrate that nearly 100 % of cells had bound particles and that the no. of bound particles was reduced by â?¼20% when PEG is also conjugated to the polymer coating. Targeting of anginex-conjugated particles to galectin-1 pos. cells was further confirmed using darkfield and photoacoustic microscopy. The untargeted particle was found to be a potent radiosensitizer, and anginex conjugation increased this effect resulting in a 4-fold redn. of surviving colonies. Photothermal heating of the nanocages was used to induce local hyperthermia which resulted in significant, tumor cell killing in the laser-irradiated region. The system's effect on angiogenesis is also under investigation. Overall, we find that anginex functions effectively as a targeting agent for these nanomaterials, which can be detected multiple ways and can be used to enhance a variety of therapeutic modalities.