Protein cage nanostructure as drug delivery system: magnifying glass on apoferritin

ABSTRACT

Introduction: New frontiers in nanomedicine are moving towards the research of new biomaterials. Apoferritin (APO), is a uniform regular self-assemblies nano-sized protein with excellent biocompatibility and a unique structure that affords it the ability to stabilize small active molecules in its inner core.

Areas covered: APO can be loaded by applying a passive process (mainly used for ions and metals) or by a unique formulative approach based on disassemby/reassembly process. In this article, we aim to organize the experimental evidence provided by a number of studies on the loading, release and targeting. Attention is initially focused on the most investigated antineoplastic drug and contrast agents up to the most recent application in gene therapy.

Expert opinion: Various preclinical studies have demonstrated that APO improved the potency and selectivity of some chemotherapeutics. However, in order to translate the use of APO into therapy, some issues must be solved, especially regarding the reproducibility of the loading protocol used, the optimization of nanocarrier characterization, detailed understanding of the final structure of loaded APO, and the real mechanism and timing of drug release.

KEYWORDS:

• Apoferritin
• chemotherapeutics
• disassembly/reassembly
• nano-cage
• passive loading
• structural characterization

Article highlights

• APO is a self-assembled molecule highly conserved in mammalian and with a high biocompatibility.

• APO offers the possibility to guest within its inner core drugs of low molecular weight and positively charged. The mechanism of drug loading can follow passive absorption/penetration processes or pH-dependent disassembly/reassembly protocols.

• Only a limited number of drugs (mainly chemotherapeutics containing metals or anthracycline) are successfully loaded into APO, showing promising results in preclinical animal models.

• APO is characterized by long lifetime and innate affinity for tumor cells due to its ability to bind human TtR1 receptor, over-expressed on cells in rapid proliferation.

Modern biotechnological approaches lead to the production of recombinant protein able to link molecules (active and/or targeting agents) directly to the protein structure, thus improving the efficacy of loaded APO and expanding its applicability to different field of therapy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was partially financed by FAR UNIMORE grants (MA Vandelli and GTosi) by University of Modena and Reggio Emilia.