Comparative whole corona fingerprinting and protein adsorption thermodynamics of PLGA and PCL nanoparticles in human serum

Abstract

Nanoparticles (NPs) based on biocompatible and biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) represent effective systems for systemic drug delivery. Upon injection into the blood circuit, the NP surface is rapidly modified due to adsorption of proteins that form a 'protein corona' (PC). The PC plays an important role in cellular targeting, uptake and NP bio-distribution. Hence, the study of interactions between NPs and serum proteins appears as key for biomedical applications and safety of NPs. In the present work, we report on the comparative protein fluorescence quenching extent, thermodynamics of protein binding and identification of proteins in the soft and hard corona layers of PLGA and PCL NPs. NPs were prepared via a single emulsionsolvent evaporation technique and characterized with respect to size, zeta potential, surface morphology and hydrophobicity. Protein fluorescence quenching experiments were performed against human serum albumin. The thermodynamics of serum protein binding onto the NPs was studied using isothermal titration calorimetry. Semi-quantitative analysis of proteins in the PC layers was conducted using gel electrophoresis and mass spectrometry using human serum. Our results demonstrated the influence of particle hydrophobicity on the thermodynamics of protein binding. Human serum proteins bind to a greater extent and with greater affinity to PCL NPs than PLGA NPs. Several proteins were detected in the hard and soft corona of the NPs, representing their unique proteome fingerprints. Some proteins were unique to the PCL NPs. We anticipate that our findings will assist with rational design of polymeric NPs for effective drug delivery applications.

Polymeric Nanoparticles with a Sera-Derived Coating for Efficient Cancer Cell Uptake and Killing

“…This was the case with NPs formed using other polymers like PLGA or polycaprolactone (PCL) in which unique nano-proteome fingerprints were detected depending on the polymer used. 53 PLGA-NPs bound human sera proteins with lower affinity compared to PCL-NPs, which adsorbed distinct proteins. The concept that NPs can be functionalized with natural materials, such as by protein adsorption, 54 is emerging as a viable approach for improving bioavailability.…”

“…To this end, the physio-chemistry of HBPE-NPs could lead to the discovery of novel sera-derived factors as indicated by our findings. This was the case with NPs formed using other polymers like PLGA or polycaprolactone (PCL) in which unique nano-proteome fingerprints were detected depending on the polymer used . PLGA-NPs bound human sera proteins with lower affinity compared to PCL-NPs, which adsorbed distinct proteins.…”

Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines

“…Additionally, PLGA NPs circulating in blood are subjected to opsonization, a process that involves the surface adsorption of serum proteins, known as opsonins, which include complement compounds, immunoglobulins, fibronectin, and apolipoproteins [ 56 ]. The adsorption of opsonins to the particle surface can occur through a number of events, including hydrophobic interactions, and, to a lesser extent, electrostatic interactions and hydrogen bonding [ 57 , 58 ]. As a result, opsonized PLGA NPs are more readily recognized and captured by cells in the MPS, which overexpress a variety of opsonin-recognizing receptors, including complement, Fc, and fibronectin receptors [ 56 ].…”

Rosmarinic Acid-Loaded Polymeric Nanoparticles Prepared by Low-Energy Nano-Emulsion Templating: Formulation, Biophysical Characterization, and In Vitro Studies

“…Consequently, a full understanding of the effect of such corona on the stability of NPs is essential for the appropriate design of nanotherapeutics. The formation of PC NPs between polymeric NPs (e.g., PLGA and PLGA-PEG) with plasma proteins (FBS), their biophysical characterization, and isolation have been reported [60,[62][63][64][65][66]. In these studies, NPs were mainly prepared via solvent emulsification-diffusion methods [66] using PVA as a stabilizer together with the use of high-energy methods (e.g., ultracentrifugation or high-speed homogenizer).…”