RESUMEN
Radiolabeling and nuclear imaging techniques are used to investigate the biodistribution patterns of the soft and hard protein corona around poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) after administration to healthy mice. Soft and hard protein coronas of 131I-labeled BSA or 131I-labeled serum are formed on PLGA NPs functionalized with either polyehtylenimine (PEI) or bovine serum albumin (BSA). The exchangeability of hard and soft corona is assessed in vitro by gamma counting exposing PLGA NPs with corona to non-labeled BSA, serum, or simulated body fluid. PEI PLGA NPs form larger and more stable coronas than BSA PLGA NPs. Soft coronas are more exchangeable than hard ones. The in vivo fate of PEI PLGA NPs coated with preformed 18F-labeled BSA hard and soft coronas is assessed by positron emission tomography (PET) following intravenous administration. While the soft corona shows a biodistribution similar to free 18F BSA with high activity in blood and kidney, the hard corona follows patterns characteristic of nanoparticles, accumulating in the lungs, liver, and spleen. These results show that in vivo fates of soft and hard corona are different, and that soft corona is more easily exchanged with proteins from the body, while hard corona is largely retained on the nanoparticle surface.
RESUMEN
Triple-negative breast cancer (TNBC) diagnosis remains challenging without expressing critical receptors. Cancer cell membrane (CCm) coating has been extensively studied for targeted cancer diagnostics due to attractive features such as good biocompatibility and homotypic tumor-targeting. However, the present study found that widely used CCm coating approaches, such as extrusion, were not applicable for functionalizing irregularly shaped nanoparticles (NPs), such as porous silicon (PSi). To tackle this challenge, we proposed a novel approach that employs polyethylene glycol (PEG)-assisted membrane coating, wherein PEG and CCm are respectively functionalized on PSi NPs through chemical conjugation and physical absorption. Meanwhile, the PSi NPs were grafted with the bisphosphonate (BP) molecules for radiolabeling. Thanks to the good chelating ability of BP and homotypic tumor targeting of cancer CCm coating, a novel PSi-based contrast agent (CCm-PEG-89Zr-BP-PSi) was developed for targeted positron emission tomography (PET)/computed tomography (CT) imaging of TNBC. The novel imaging agent showed good radiochemical purity (â¼99 %) and stability (â¼95 % in PBS and â¼99 % in cell medium after 48 h). Furthermore, the CCm-PEG-89Zr-BP-PSi NPs had efficient homotypic targeting ability in vitro and in vivo for TNBC. These findings demonstrate a versatile biomimetic coating method to prepare novel NPs for tumor-targeted diagnosis.
