Abstract

Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One of the main favorable characteristics of FNs is their intrinsic targeting efficiency toward the Transferrin Receptor 1, which is overexpressed in many tumors. Furthermore, genetic manipulation can be employed to introduce novel variants that are able to improve the loading capacity, targeting capabilities and bio-availability of this versatile drug delivery system. In this review, we discuss the main characteristics of FN and the most recent applications of this promising nanotechnology in the field of oncology with a particular emphasis on the imaging and treatment of solid tumors.

Highlights

  • Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities

  • An exception is represented by virus-like particles (VLPs), which are composed of self-assembled proteins that are, in some cases, highly immunogenic [5]

  • ferritin nanocages (FNs) have been studied extensively due to their intrinsic targeting capabilities toward the Transferrin Receptor 1 (TfR1), which is highly expressed in many tumors, making them very appealing for drug-delivery applications in oncology

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Summary

Introduction

Nanoparticle-based drug delivery systems have the capacity to enhance the physicochemical properties of a wide variety of drugs used in oncology to limit off-site side effects and improve their therapeutic efficacy [1,2,3]. Some examples are ferritin nanocages (FNs), heat-shock protein cages, vault ribonucleoparticles, the E2 protein of the pyruvate dehydrogenase multienzyme complex, chaperones, carboxysomes and other enzyme complexes [6] Most of these protein-based NP are understudied and have, so far, limited applications in the field of oncology. Extreme pH (2 or 13) is used to transiently disassemble the protein nanocage into monomers that can reassemble by adjusting the pH toward neutrality By employing this methodology, FN can be loaded with different chemotherapeutic drugs. High concentrations of guanidine hydrochloride (GuHCl) or urea are able to disrupt the non-covalent forces which support FNs’ structure, leading to their disassembly This process can be reversed by dialysis to remove the excess of chaotropic agents, leading to the recovery of the original nanostructure with consequent loading of molecular cargoes in the inner cavity [24].

Biochemical
Production and Modifications of FN
FN-Based NPs for Cancer Treatment in Preclinical Models
FN-Based NPs
FN-Based NPs for the Treatment of Brain Tumors
Preclinical Exploitation of FN-Based NPs for Tumor Imaging
Findings
Drawbacks and Future Perspective of FN
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