How can we predict behavior of nanoparticles in vivo?

Abstract

The emergence of nanotechnology and nanoparticles has brought conceptually new possibilities for administration of therapeutic agents. Sustained release, targeting, altered pharmacokinetic, reduced toxicity and increased drug bioavailability make nanoscale drug delivery systems highly attractive for improving the therapeutic index of many drugs. It is quite striking that nanotechnology not simply represents a miniaturization of larger objects, but rather enables preparation of materials at the nanometric scale with physical and chemical properties which dramatically differ from those of bulk materials. The main reason for this remarkable change in nanomaterial behavior is its enormous surface-to-volume ratio, which provides a very large interfacial surface area as driving force for enhanced interaction of nanomaterial with surrounding it molecules. Therefore, upon intravenous administration, nanoparticles inevitably form layers of adsorbed biomolecules (mainly proteins) known as a ‘protein corona’ [1,2]. The adsorption of proteins on the surface of nanoparticle is regulated by protein-nanoparticle binding affinity and by protein–protein interactions. Proteins that directly adsorb to the nanoparticle surface with high affinity (usually characterized by long desorption rates in the order of several hours [3]) form the first layer of tightly bound proteins known as the ‘hard corona’. There is a second stage, which consists of proteins interacting with this firmly bound proteinnanoparticle complex via low-affinity protein–protein interactions, forming the socalled ‘soft corona’ and consisting of loosely bound proteins. The complex structure of protein corona alters the size and interfacial composition of nanoparticles, conferring them a new biological identity, which is what is ‘seen’ by cells in reality. The biological identity of nanoparticles, which could be significantly different from their original synthetic identity, determines the physiological behavior of nanoparticles influencing their colloidal stability, targeting capability, kinetics of circulation, transport, cellular uptake and organ accumulation, degradation, drug release, signaling and toxicity [4]. Because the relative quantities of the adsorbed proteins on the surface of nanoparticles do not necessarily correlate with their abundance in blood plasma, the composition of protein corona for each particular type of nanomaterial is unique and influenced by multiple factors. The complexity and uniqueness of the protein corona composition in each particular case of nanomaterial does not allow one to reliably predict behavior of nanomaterials in vivo, which remains one of the major challenges in achieving a predictable and safe use of nanoparticlebased drug delivery systems in therapeutic applications. How can we predict behavior of nanoparticles in vivo?