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

Abstract

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.

Development of novel apoferritin formulations for antitumour benzothiazoles

“…Of particular interest is protein capsule apoferritin (AFt), which has been successfully used for development of biohybrid and self-assembled materials, 1,2 for the encapsulation of proteins 3 and small drug molecules. [4][5][6][7][8] AFt consists of 24 polypeptide subunits assembled into a spherical protein cage with an internal cavity of 8 nm in diameter 9 ; 0.3-to 0.4-nm channels in the shell 10 and pH-dependent dissembly 9 allow controlled release of cargo. The uniform size, biocompatibility, biodegradability, and non-toxicity has led to AFt being identified as an ideal drug delivery vehicle.…”

Ferritin: A Platform for MRI Contrast Agents Delivery

“…with the size of commonly used CAs (8-9 Å ) [28]. Different strategies for trapping small molecules in the apoferritin core were reported [29]. The procedure first indicated by Aime and coworkers [30] consisted of the dissociation of horse spleen apoferritin (HoS-apoferritin) into subunits at pH 2 followed by its reassociation at pH 7.4.…”

“…10 Gd-2,2′,2″-[10-(2hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl]triacetic acid (Gd-HPDO3A) units per apoferritin molecule (Gd-Apo). Gd-HPDO3A ( Figure 2C) is a commercially available (trade name Different strategies for trapping small molecules in the apoferritin core were reported [29]. The procedure first indicated by Aime and coworkers [30] consisted of the dissociation of horse spleen apoferritin (HoS-apoferritin) into subunits at pH 2 followed by its reassociation at pH 7.4.…”

“…In particular, ferritin, due to properties such as its high stability and biocompatibility, has emerged also as an excellent and promising drug carrier [67]. Although Doxorubicin encapsulation in ferritin nanocages represents the most extensively investigated system [29,68,69], there are also some interesting results reporting the efficacy of the encapsulated Cisplatin [70][71][72]. Several studies have provided strong evidence of an enhanced efficacy of chemotherapeutic therapy after their encapsulation in ferritin-based nanoparticles, not only for anticancer drugs, but also for other active molecules [29].…”

“…Although Doxorubicin encapsulation in ferritin nanocages represents the most extensively investigated system [29,68,69], there are also some interesting results reporting the efficacy of the encapsulated Cisplatin [70][71][72]. Several studies have provided strong evidence of an enhanced efficacy of chemotherapeutic therapy after their encapsulation in ferritin-based nanoparticles, not only for anticancer drugs, but also for other active molecules [29]. The first example of the use of apoferritin to deliver therapeutic and imaging agents simultaneously was proposed to target hepatocytes by SCARA5 via the ferritin-transporting route [73].…”