To date, the translation of Au (III) complexes into chemotherapeutic agents has been hindered by their low stability under physiological conditions, a crucial parameter in drug development. In this study, we report an innovative four-step synthesis of a stable Au (III)-doxorubicin (DOX) complex, acting as a key constitutive component of doxorubicin-loaded PEG-coated nanoparticles (DOX IN-PEG-AuNPs). For therapeutic purposes, such AuNPs were then functionalized with the anti-Kv11.1 polyclonal antibody (pAb), which specifically recognizes the hERG1 channel that is overexpressed on the membrane of human pancreatic cancer cells. The nature of the interactions between DOX and Au (III) ions was probed by various analytical techniques (Raman spectroscopy, UV-vis, and (1)H NMR), which enabled studying the Au (III)-DOX interactions during AuNPs formation. The theoretical characterization of the vibrational bands and the electronic transitions of the Au (III)-DOX complex calculated through computational studies showed significant qualitative agreement with the experimental observations on AuNPs samples. Stability in physiological conditions and efficient drug loading (up to to 85 w/w %) were achieved, while drug release was strongly dependent on the structure of DOX IN-PEG-AuNPs and on the pH. Furthermore, the interactions among DOX, PEG, and Au (III) ions in DOX IN-PEG-AuNPs differed significantly from those found in polymer-modified AuNPs loaded with DOX by covalent linkage, referred to as DOX ON-PEG-AuNPs. In vitro experiments indeed demonstrated that such differences strongly influenced the therapeutic potential of AuNPs in pancreatic cancer treatment, with a significant increase of the DOX therapeutic index when complexed to Au (III) ions. Collectively, our study demonstrated that Au (III)-DOX complexes as building blocks of PEGylated AuNPs constitutes a promising approach to transform promising Au (III) complexes into real chemotherapeutic drugs for the treatment of pancreatic cancer.

Fluorescence is a very promising radioactive-free technique for functional imaging in small animals and, in the future, in humans. However, most commercial near-infrared dyes display poor optical properties, such as low fluorescence quantum yields and short fluorescence lifetimes. In this paper, we explore whether the encapsulation of infrared cyanine dyes within the core of lipid nanoparticles (LNPs) could improve their optical properties. Lipophilic dialkylcarbocyanines DiD and DiR are loaded very efficiently in 30-35-nm-diam lipid droplets stabilized in water by surfactants. No significant fluorescence autoquenching is observed up to 53 dyes per particle. Encapsulated in LNP, which are stable for more than one year at room temperature in HBS buffer (HEPES 0.02 M, EDTA 0.01 M, pH 5.5), DiD and DiR display far improved fluorescence quantum yields Phi (respectively, 0.38 and 0.25) and longer fluorescence lifetimes tau (respectively, 1.8 and 1.1 ns) in comparison to their hydrophilic counterparts Cy5 (Phi=0.28, tau=1.0 ns) and Cy7 (Phi=0.13, tau=0.57 ns). Moreover, dye-loaded LNPs are able to accumulate passively in various subcutaneous tumors in mice, thanks to the enhanced permeability and retention effect. These new fluorescent nanoparticles therefore appear as very promising labels for in vivo fluorescence imaging.