Engineering protein self-assembling in protein-based nanomedicines for drug delivery and gene therapy

Abstract

Lack of targeting and improper biodistribution are major flaws in current drug-based therapies that prevent reaching high local concentrations of the therapeutic agent. Such weaknesses impose the administration of high drug doses, resulting in undesired side effects, limited efficacy and enhanced production costs. Currently, missing nanosized containers, functionalized for specific cell targeting will be then highly convenient for the controlled delivery of both conventional and innovative drugs. In an attempt to fill this gap, health-focused nanotechnologies have put under screening a growing spectrum of materials as potential components of nanocages, whose properties can be tuned during fabrication. However, most of these materials pose severe biocompatibility concerns. We review in this study how proteins, the most versatile functional macromolecules, can be conveniently exploited and adapted by conventional genetic engineering as efficient building blocks of fully compatible nanoparticles for drug delivery and how selected biological activities can be recruited to mimic viral behavior during infection. Although engineering of protein self-assembling is still excluded from fully rational approaches, the exploitation of protein nano-assemblies occurring in nature and the direct manipulation of protein–protein contacts in bioinspired constructs open intriguing possibilities for further development. These methodologies empower the construction of new and potent vehicles that offer promise as true artificial viruses for efficient and safe nanomedical applications.

• Drug delivery
• nanomedicine
• nanoparticles
• non-viral gene therapy
• protein engineering

Acknowledgements

We are indebted to MINECO (BFU2010-17450, ACI2009-0919 and IT2009-0021), AGAUR (2009SGR-0108), FISS (PS09-00165 and PI12-00327) and CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, Spain) for funding our research on protein-based nanotherapeutics. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. EGF is supported by the Programa Personal de Técnico de Apoyo (Modalidad Infraestructuras científico-tecnológicas, MICINN). AV received an ICREA ACADEMIA award.

Declaration of interest

The authors report no declarations of interest.