UNDERSTANDING THE EFFECTS OF THE PROTEIN CORONA ON NANOPARTICLE PERMEABILITY WITH AN IN VITRO MICROFLUIDIC PLATFORM FOR VASCULAR PERMEABILITY
Yan Teck Ho1,2, Nurul Ain Azman1, Giulia Adriani3, Sebastian Beyer3, Roger D Kamm2,4, Phan-Thien Nhan1, James Chen Yong Kah1
1National University of Singapore, Singapore;
2Singapore-MIT Alliance for Research and Technology, Singapore;
3Singapore MIT Alliance for Research and Technology, Singapore;
4Massachusetts Institute of Technology, USA
Recent work in nanoparticle (NP) drug delivery systems has seen efforts in using the protein corona as an indigenous vector for payload loading and delivery. Translational efforts however have seen obstacles arising in part from the lack of understanding in how the corona can affect NP permeability when introduced in vivo, which in turn could have a profound effect on the NP’s drug delivery efficacy and efficiency. By studying the aggregation profile of protein coronas formed from four major constituent proteins – apolipoprotein-A1, albumin, fibrinogen, and immunoglobulin-G – in serum on gold NPs, we observed through measurements of the NP’s aggregation index and hydrodynamic diameter that the corona leads to NP aggregation in a manner dependent on protein concentration and its physiological function in vivo. Furthermore, evidence in the literature suggests that the presence of a protein corona can also affect a NP’s cellular uptake. Taken together, the corona could therefore have a profound effect on a NP’s para and trans-cellular permeability. To investigate this, we have successfully developed an in vitro microfluidic platform for probing NP permeability with human umbilical vein endothelial cells (HUVECs) cultured in the device. Using 10 and 70 kDa dextran as model probe molecules, we successfully demonstrated the tunability of HUVECs permeability with angiopoietin-1 (Ang-1) and cyclic adenosine monophosphate (pCPT-cAMP) treatment. Untreated and 25 μg/mL pCPT-cAMP treated devices were also shown to approximate cancer and normal physiological permeability values obtained in vivo respectively. Probing the permeability of polystyrene NPs with both untreated and 25 μg/mL pCPT-cAMP devices also yielded a non-linearly decreasing trend with increasing particle size similarly observed in in vivo systems. Our developed platform could therefore be used to provide valuable insight into NP-corona systems that could help promote through better design, the translation of NP based systems in vivo.