Regulation of nano-biological interface adhesion through grafted polymers

Abstract

<p indent="0mm">The employment of grafted polymers to modulate the adhesion behavior of nano-biological interfaces has a wide range of applications in the field of biomedicine, and related research has important theoretical significance, thus gaining continuous attention. In this paper, the physicochemical mechanisms involved in the regulation of the adhesion behaviors of the nano-biological interface by grafted polymers are reviewed. There are two key challenges in the field of nanomedicine: Suppressing of immune responses and enhancing the drug retention at disease sites. In the both aspects, grafted polymers play an increasingly important role. By grafting polymers on the surface of nano-drugs, the random adhesion of small biomolecules can be suppressed, thereby decreasing the thickness of protein coronas, reducing the immune response, and prolonging the <italic>in vivo</italic> circulation time. Reduced adhesion also alleviates the dissipation of nano-drugs. In addition, grafted polymers can alter the surface mechanical property, endowing a moderate stiffness and altering collision behaviors, thus enhancing the transport efficiency and nano-drugs in physiological tissues and nano-drug retention at disease sites. The involved mechanisms in this paper are divided into two categories: Interfacial physics and interfacial chemistry. The former group mainly focuses on the microstructure and morphology, which can be adjusted through grafting density, grafting length, chain topology, etc. This paper focuses on two physical mechanisms closely related to the high entropy properties of grafted polymers: Entropic steric hindrance and chain segment dynamics. With increasing grafting density, the repulsive interactions between grafted chains increase, and the chains are stretched further resulting in a thicker grafting layer. Meanwhile, the conformation of grafting polymers experiences a mushroom-to-brush transition. In addition to less free volume, a higher grafting density also enhances chain stiffness, making biomolecules encounter a higher steric repulsive force when colliding with grafting polymer chains and thus less biomolecule adhesion. A high mobility of segmental chains also suppresses adhesion. According to this mechanism, increasing grafting density decreases segmental chain dynamics and promotes adhesion. The two mechanisms compete with increasing grafting density. Entropic steric hindrance dominates in low grafting density regime, while chain segment dynamic plays a larger role in high grafting density regime. A moderate high grafting density has maximal inhibiting ability on adhesion. The regulation of biomolecule adhesion based on interfacial physics combines structural and dynamical factors, and is usually nonspecific, although specific regulation is also possible. This group of mechanisms is independent of specific chemical groups, thus having a certain degree of universality. The mechanisms based on interfacial chemistry depend on special chemical groups, especially the hydrophilicity of functional groups. Most grafted polymers having good anti-fouling properties are hydrophilic, for example, polyethylene glycol (PEG). Hydrophilic functional groups promote the formation of hydrated surface layers, which inhibit biomolecule adhesion. PEG is the most widely used by now. However, its stability and anti-fouling ability are limited. By finding and modifying with appropriate chemical groups on the grafted chains, a better stability and stronger inhabitation of biomolecule adhesion can be achieved. On the other hand, through adjusting the temperature, light or pH dependence of chemical groups, the bio-adhesion of the grafting polymer layer can be dynamically tuned, realizing intelligent response to external stimuli and thus smart coating surfaces. This paper is expected to provide a reference for future fundamental theoretical research and advanced material development in this field.