Silica-Based Nanoparticles for Protein Encapsulation and Delivery.

Filippo Begarani,Valerio Voliani,Domenico Cassano,Roberto Marotta,Eleonora Margheritis,Francesco Cardarelli

doi:10.3390/nano8110886

Abstract

Although conceptually obvious, the effective delivery of proteins in therapeutic applications is far from being a routine practice. The major limitation is the conservation of protein physicochemical identity during the transport to the target site. In this regard, nanoparticle-based systems offer new intriguing possibilities, provided that (i) the harsh and denaturating conditions typically used for nanoparticle synthesis are avoided or mitigated; and (ii) nanoparticle biocompatibility and degradation (for protein release) are optimized. Here, we tackle these issues by starting from a nanoparticle architecture already tested for small chemical compounds. In particular, silica-shielded liposomes are produced and loaded with a test protein (i.e., Green Fluorescent Protein) in an aqueous environment. We demonstrate promising results concerning protein encapsulation, protection during intracellular trafficking and final release triggered by nanoparticle degradations in acidic organelles. We believe this proof of principle may open new applications and developments for targeted and efficient protein delivery.

Highlights

Protein-based therapeutic strategies are currently being actively researched for the treatment of a variety of diseases [1,2,3]
Nanoparticles can be functionalized with different materials/molecules tailored to different scopes: they can possess biomimetic surfaces [11,12], pH-responsive moieties [13] or targeting tools, such as antibodies, peptides or small molecules [14]
The synthesis of the proposed nanoparticles began with the formation of liposomes and their loading with AcGFP dissolved in a diethanolamine (DEA) buffer solution

Summary

Introduction

Protein-based therapeutic strategies are currently being actively researched for the treatment of a variety of diseases [1,2,3]. Proteins typically possess a peculiar set of specific roles, which are not mimicked by other chemical compounds This high functional specificity gives protein therapeutics fewer chances to interfere with other off-target biological processes, reducing adverse/aspecific responses. In light of these benefits, one may expected reduced times for the clinical approval of protein-based therapeutic compounds as compared to small-molecule drugs [3]. For instance, favoring protein circulation half-life, proved to be extremely complex, often ending up in unwanted protein conformational changes (that in turn impair the desired functions [8]) Genetic engineering, such as the creation of Fc-based fusion proteins (made by linking an immunoglobulin Fc domain to the therapeutic protein), greatly contributed to enhancing protein half-life and their therapeutic efficacy. We shall present the approach for the production and loading of the nanoparticles along with confocal imaging analysis of their trafficking and final fate when administered to living cells

Methods

Results

Conclusion