RGD-Modified Apoferritin Nanoparticles for Efficient Drug Delivery to Tumors

Abstract

Ferritin is a major iron storage protein found in humans and most living organisms. Each ferritin is comprised of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD integrin αvβ3 interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein we showed that after being pre-complexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49wt%). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.

H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

“…Recently, it was reported that HFn binds to human cells via interacting with the transferrin receptor 1 (TfR1) (11). Although it is well known that TfR1 is highly expressed on human cancer cells and has long been used as a targeting marker for tumor diagnosis and therapy, current HFn-based methods for tumor detection and treatment still rely on functionalization of HFn with recognition ligands to achieve tumorspecific targeting (12)(13)(14)(15)(16).…”

“…Although ferritin-based drug delivery has been recently developed for cancer treatment, in almost all published studies ferritin was modified with recognition ligands to achieve tumorspecific targeting (12)(13)(14)(15). These extra surface modifications destroy the intrinsic tumor-specific binding of natural ferritin and disturb its in vivo performance and biocompatibility because of the altered surface physicochemical properties of ferritin.…”

An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

“…[ 12,13 ] The unique architecture of AFt provides two interfaces: the outer surface of AFt can be modifi ed chemically or genetically with functional motifs [ 14 ] and the internal cavity can be used to encapsulate pharmaceutical agents such as anticancer drugs, magnetic resonance imaging (MRI), and fl uorescent imaging agents. [ 6,9,15,16 ] Recently, selective targeting and cargo delivery with heavy chain apoferritin (H-AFt) was demonstrated both in vitro [ 17 ] and in vivo.…”

A Hollow NaGdF4/AFn Nanosystem Based on “Relay Race” Release for Therapy

“…At time points established in advance (5 and 10 min, and 0. 5,1,2,4,8,12,24,36, and 48 h), buffer solution was removed (1 mL) and fresh buffer was added back to the system. and 48 h), buffer solution was removed (1 mL) and fresh buffer was added back to the system.…”