Engineered Ferritin Nanoparticles for the Bioluminescence Tracking of Nanodrug Delivery in Cancer

Abstract

The identification of a highly sensitive method to check the delivery of administered nanodrugs into the tumor cells is a crucial step of preclinical studies aimed to develop new nanoformulated cures, since it allows the real therapeutic potential of these devices to be forecast. In the present work, the ability of an H‐ferritin (HFn) nanocage, already investigated as a powerful tool for cancer therapy thanks to its ability to actively interact with the transferrin receptor 1, to act as an efficient probe for the monitoring of nanodrug delivery to tumors is demonstrated. The final formulation is a bioluminescent nanoparticle, where the luciferin probe is conjugated on nanoparticle surface by means of a disulfide containing linker (Luc‐linker@HFn) which is subjected to glutathione‐induced cyclization in tumor cell cytoplasm. The prolonged imaging of luciferase+ tumor models, demonstrated by an in vitro and an in vivo approach, associated with the prolonged release of luciferin into cancer cells by disulfide bridge reduction, clearly indicates the high efficiency of Luc‐linker@HFn for drug delivery to the tumor tissues.

Integrin α2β1-targeting ferritin nanocarrier traverses the blood–brain barrier for effective glioma chemotherapy

“…However, in addition to the wide binding specificity of a variety of integrins, it has been reported that repeated administration of integrin αvβ3-targeting RGD peptides would most likely trigger immunogenicity [ 44 ]. Furthermore, the distribution and number of the targeting ligands, Arg-Gly-Asp (RGD), modified on the ferritin nanocarrier surface have the significant impact on efficacy of active tumor targeting [ 45 ]. The surface ligand pattern should be optimized to fit the receptor clustering feature to achieve the best tumor targeting.…”

A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

“…As the globally commercialized CSFV lapinized vaccine strain C failed in serological DIVA (differentiation between infected and vaccinated animals), the application of a novel ferritin nanoplatform with soluble E2 antigen provides a candidate for vaccine development for the eradication of the CSFV pandemic. Numerous self-assembling ferritin-associated studies showed that the exposed antigens or proteins were produced in native status and arranged in well-ordered manners, such as a bioluminescent tracer for liver cancer detection and receptor binding domain decoration for COVID-19 elimination [28,29]. Furthermore, the 24-subunit polymer was efficiently phagocytosed by body antigen recognition and presentation systems with a sensitive and potent neutralizing antibody response in vivo (see Figure 3a).…”

“…The nanoparticles were bound and purified using an Ni-NTA affinity column [28]. The sample supernatant was loaded at a rate of 1.0 mL/min, and the column was washed with 5 column volumes (CV) of buffer A (0.1 M PBS, 300 mM NaCl, 5 mM imidazole) at 1 mL/min.…”

Protein nanoparticles directed cancer imaging and therapy

“…Intracellular GSH can break the disulfide bond and release free luciferin. Luciferin is able to react with luciferase and perform bioluminescence imaging [173] modified iron oxide nanoparticles was rich in amine groups. Compact HSA coating could be realized just by adsorbing due to the natural multivalency and good solubility of protein-based nanoparticles.…”