Seedless Synthesis of Disulfide-Grafted Gold Nanoflowers with Size and Shape Control and Their Photothermally Mediated Cell Perforation

Thiol-based ligands have been widely used for passivating metal nanoparticles (NPs) to impart a variety of surface properties while maintaining high colloidal stability. However, their use in direct NP synthesis has been limited to small size (<15 nm) with spherical shape, and direct synthesis of anisotropic gold NPs using dithiol- or disulfide-based ligands has not been achieved. Here, we demonstrate a novel one-step method for the synthesis of multipod-shaped gold NPs (gold nanoflower; AuNF) with a wide size regime (20-500 nm) by controlling the reducing power, acidity, and reagent stoichiometry during NP synthesis using thioctic acid (TA). This strategy is also applied for derivatives of TA-based ligands (e.g., varied terminal groups and the length) to modulate the physicochemical function of AuNFs. To our knowledge, this is the first systematic study of seedless synthesis of anisotropic AuNPs using disulfide-based multifunctional ligands. The resulted morphological anisotropy, created by multiple lobes of "pods" of AuNFs, expands the surface plasmon resonance (SPR) absorption beyond 650 nm, which is longer than the SPR band of gold nanospheres with similar size. The significant red shift of a AuNF SPR band is evaluated by electromagnetic simulations using the finite-element method. We then demonstrate that cholesterol-modified 20 nm AuNFs efficiently convert the 640 nm excitation light to localized heat and perforate the cellular membrane to deliver cellimpermeable molecules (ethidium homodimer-1). Our approach provides a pathway to surfactantless and one-step formation of anisotropic nanostructures using disulfide-based ligands. Their improved photothermal effect under long-wavelength excitation can be used for cell perforation and direct cytosol delivery of various molecules.