Anginex is an antiangiogenic, synthetic 33mer that binds to galectin-1, which is overexpressed by the tumor endothelium – a critical requirement for effective nanomedicine delivery – as well as by tumor cells themselves. In the present study, anginex was used as a targeting agent after conjugation to polydopamine-coated Au nanocages, which were selected for their photothermal conversion, biocompatibility, and functionalization potential. Approximately 6x10<sup>4</sup> peptides were conjugated to each particle, which caused the zeta potential to change from highly negative to moderately positive. Cellular targeting was confirmed by darkfield microscopy, photoacoustic microscopy, and photoacoustic flow cytometry. In vitro photothermal cell killing was observed despite the temperature within the well remaining below 40 °C. The peptide retained its biological activity after conjugation, as demonstrated by migration and tube-formation assays, which indicated similar effects caused by free peptide or nanoparticle-bound peptide. Additionally, the construct affected zebrafish development in a manner similar to inhibitors of neovascularization. Murine breast tumors were grown in immunocompetent mice, and the construct was introduced intravenously. The particle concentration in circulation was monitored photoacoustically, and the clearance was found to be biphasic with a residual amount of particles still circulating after 24 h. Little outward sign of toxicity was observed in mice. Anginex enabled these nanocages to specifically target and remain in tumor tissue resulting in a 3 fold increase in tumor accumulation compared to non-targeted nanocages, which was visualized by photoacoustic imaging and confirmed with mass analysis. Subsequently, a ten minute irradiation with a continuous wave laser was used to heat the tumor to a mean temperature of roughly 43 °C, which resulted in significant retardation of tumor growth. The tumors were excised, and the distribution of the particles within the tumor tissue itself was determined, which informed the mechanism for the effectiveness of the treatment. These studies demonstrate the potential of anginex as a targeting agent for theranostic nanomedicines.

Local-mapping and photothermal tumor treatment using galectin-1 targeting nanomaterials

255th National Meeting (2018)

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