Polypeptide-based multilayer nanoarchitectures: Controlled assembly on planar and colloidal substrates for biomedical applications

Abstract

Polypeptides have shown an excellent potential in nanomedicine thanks to their biocompatibility, biodegradability, high functionality, and responsiveness to several stimuli. Polypeptides exhibit high propensity to organize at the supramolecular level; hence, they have been extensively considered as building blocks in the layer-by-layer (LbL) assembly. The LbL technique is a highly versatile methodology, which involves the sequential assembly of building blocks, mainly driven by electrostatic interactions, onto planar or colloidal templates to fabricate sophisticated multilayer nanoarchitectures. The simplicity and the mild conditions required in the LbL approach have led to the inclusion of biopolymers and bioactive molecules for the fabrication of a wide spectrum of biodegradable, biocompatible, and precisely engineered multilayer films for biomedical applications. This review focuses on those examples in which polypeptides have been used as building blocks of multilayer nanoarchitectures for tissue engineering and drug delivery applications, highlighting the characteristics of the polypeptides and the strategies adopted to increase the stability of the multilayer film. Cross-linking is presented as a powerful strategy to enhance the stability and stiffness of the multilayer network, which is a fundamental requirement for biomedical applications. For example, in tissue engineering, a stiff multilayer coating, the presence of adhesion promoters, and/or bioactive molecules boost the adhesion, growth, and differentiation of cells. On the contrary, antimicrobial coatings should repel and inhibit the growth of bacteria. In drug delivery applications, mainly focused on particles and capsules at the micro- and nano-meter scale, the stability of the multilayer film is crucial in terms of retention and controlled release of the payload. Recent advances have shown the key role of the polypeptides in the adsorption of genetic material with high loading efficiency, and in addressing different pathways of the particles/capsules during the intracellular uptake, paving the way for applications in personalized medicine. Although there are a few studies, the responsiveness of the polypeptides to the pH changes, together with the inclusion of stimuli-responsive entities into the multilayer network, represents a further key factor for the development of smart drug delivery systems to promote a sustained release of therapeutics. The degradability of polypeptides may be an obstacle in certain scenarios for the controlled intracellular release of a drug once an external stimulus is applied. Nowadays, the highly engineered design of biodegradable LbL particles/capsules is oriented on the development of theranostics that, limited to use of polypeptides, are still in their infancy.