Design of PEGylated Three Ligands Silica Nanoparticles for Multi-Receptor Targeting

The synthesis of silica nanoparticles (SiNPs) decorated on their surface with a range of various elements (e.g., ligands, drugs, fluorophores, vectors, etc.) in a controlled ratio remains a big challenge. We have previously developed an efficient strategy to obtain in one-step, well-defined multifunctional fluorescent SiNPs displaying fluorophores and two peptides ligands as targeting elements, allowing selective detection of cancer cells. In this paper, we demonstrate that additional level of controlled multifunctionality can be achieved, getting even closer to the original concept of magic bullet, using solely sol-gel chemistry to achieve conjugation of PEG chains for stealth, along with three different ligands. In addition, we have answered the recurrent question of the surface ungrafting by investigating the stability of different siloxane linkages with the ERETIC Method (Electronic Reference to Access In Vivo Concentrations) by F-19 NMR quantification. We also compared the efficiency of the hybrid silylated fluorophore covalent linkage in the core of the SiNP to conventional methods. Finally, the tumor-cell-targeting efficiency of these multi-ligand NPs on human endothelial cells (HUVEC or HDMEC) and mixed spheroids of human melanoma cells and HUVEC displaying different types of receptors were evaluated in vitro.

Automated summary

This paper demonstrates the achievement of a higher level of controlled multifunctionality by using sol-gel chemistry to conjugate PEG chains and three different ligands on the core of SiNPs, while also addressing the issue of surface ungrafting. The study compares the efficiency of different linking methods and evaluates the tumor-cell-targeting efficiency of multi-ligand SiNPs in human endothelial cells and mixed spheroids in vitro.