A Versatile Brij-Linker for One-Step Preparation of Targeted Nanoparticles

Background: Most frequently the functionalization of nanoparticles is hampered by time-consuming, sometimes harsh conjugation and purification procedures causing premature drug release and/or degradation. A strategy to circumvent multi-step protocols is to synthesize building blocks with different functionalities and to use mixtures thereof for nanoparticle preparation in one step. Methods: BrijS20 was converted into an amine derivative via a carbamate linkage. The Brij-amine readily reacts with pre-activated carboxyl-containing ligands such as folic acid. The structures of the building blocks were confirmed by different spectroscopic methods and their utility was assessed by one-step preparation and characterization of nanoparticles applying PLGA as a matrix polymer. Results: Nanoparticles were about 200 nm in diameter independent of the composition. Experiments with human folate expressing single cells and monolayer revealed that the nanoparticle building block Brij mediates a stealth effect and the Brij-amine-folate a targeting effect. As compared to plain nanoparticles, the stealth effect decreased the cell interaction by 13%, but the targeting effect increased the cell interaction by 45% in the monolayer. Moreover, the targeting ligand density and thus the cell association of the nanoparticles is easily fine-tuned by selection of the initial ratio of the building blocks. Conclusions: This strategy might be a first step towards the one-step preparation of nanoparticles with tailored functionalities. Relying on a non-ionic surfactant is a versatile approach as it might be extended to other hydrophobic matrix polymers and promising targeting ligands from the biotech pipeline.

Automated summary

In this study, a one-step method was proposed for the preparation of nanoparticles with tailored functionalities. The results showed that the strategy could effectively control the targeting and stealth effects of the nanoparticles, and the initial ratio of the building blocks could easily fine-tune the ligand density and cell association.