Harnessing Buffer Solutions to Modify the Association State of Ferritin Nanoparticles
Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy
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Author to whom correspondence should be addressed.
Separations 2023, 10(7), 414; https://doi.org/10.3390/separations10070414
Submission received: 17 May 2023
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Accepted: 31 May 2023
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Published: 20 July 2023
(This article belongs to the Section Purification Technology)
1. Introduction
Recent years have witnessed remarkable progress in the field of drug delivery driven by the pursuit of efficient and targeted delivery systems [1,2]. Among the promising candidates for such systems are ferritins, nanoparticles distinguished by their unique hollow sphere structure and the ability to specifically target cell surface receptors [3,4]. In a groundbreaking study, researchers developed a chimeric ferritin protein derived from both human and archaeal sources. This innovative design incorporates the BC loop of human H ferritin, endowing the chimeric ferritin with CD71 recognition capabilities [5]. Furthermore, the researchers introduced a novel modification to the ferritin protein, enhancing its drug delivery potential by utilizing buffer solutions to finely tune its assembly and disassembly properties [6]. These advancements open up new avenues for the study of encapsulation and delivery of small therapeutic and diagnostic molecules.
2. Chimeric Ferritins: A New Frontier in Drug Delivery
Ferritins have gained recognition as excellent vehicles for drug delivery due to their inherent characteristics such as their hollow structure and receptor-targeting abilities [7,8,9,10,11]. In this study, the research team developed a novel ferritin variant derived from a chimeric humanized Archaeoglobus fulgidus protein [6]. This ingenious design facilitated the modification of the protein cage, enabling the incorporation of even small therapeutics without any risk of leakage. By substituting two positively charged amino acids with alanine residues, the large triangular pores on the protein’s surface were closed [12], rendering it an ideal container for encapsulating therapeutic agents. Moreover, the inclusion of the BC loop from human H ferritin bestowed CD71 recognition properties upon this chimeric ferritin, further enhancing its drug delivery potential [5].
3. Fine-Tuning Assembly and Disassembly with Buffer Solutions
A pivotal aspect of utilizing ferritins as drug delivery systems is the precise control of their assembly and disassembly processes. The research team discovered that by manipulating the HEPES buffer concentration and introducing MgCl2, they could easily adjust the assembly and disassembly properties of the modified ferritin protein cage. Size-exclusion chromatography was employed to demonstrate the effectiveness of this approach, showcasing the versatility of buffer solutions in manipulating the association state of ferritins. The protein cage could be opened using 150 mM HEPES buffer in the absence of magnesium ions, while the introduction of divalent magnesium ions facilitated the rapid assembly of the ferritin into its 24-mer form, thereby optimizing drug encapsulation and delivery [6].
4. Unleashing the Potential for Therapeutics and Diagnostics
The successful development and characterization of this new protein cage represent a significant milestone in the field of drug delivery. With the ability to precisely encapsulate and deliver small molecules, researchers can now explore a broad range of therapeutic and diagnostic applications. The controlled assembly and disassembly of the ferritin protein cage offer unprecedented opportunities for targeted delivery, ensuring that therapeutic agents reach their intended destinations while minimizing side effects and maximizing efficacy. Furthermore, the CD71 recognition properties of this chimeric ferritin extend its applicability to specifically target cells expressing the CD71 receptor, opening up new avenues for precision medicine.
5. Future Directions and Implications
The advent of this modified ferritin protein cage heralds a realm of possibilities for drug delivery and biomedical research. The fine-tuning capabilities of buffer solutions provide scientists with a powerful tool to optimize the assembly and disassembly of the protein cage according to specific therapeutic requirements. Additionally, the CD71 recognition properties add an extra dimension to targeted delivery strategies. This technology has the potential to revolutionize drug delivery systems by enabling the encapsulation and targeted delivery of a diverse range of therapeutic agents, with enhanced treatment efficacy and reduced adverse effects.
Author Contributions
Conceptualization: A.B. (Alessandra Bonamore) and A.M.; writing A.I. and C.C.; review and editing A.M. and A.B. (Alberto Boffi). All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Sapienza University of Rome, “SEED 2022”, grant number SP1221846100319C.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Manzari, M.T.; Shamay, Y.; Kiguchi, H.; Rosen, N.; Scaltriti, M.; Heller, D.A. Targeted drug delivery strategies for precision medicines. Nat. Rev. Mater. 2021, 6, 351–370. [Google Scholar] [CrossRef]
- Mansour, A.; Romani, M.; Acharya, A.B.; Rahman, B.; Verron, E.; Badran, Z. Drug Delivery Systems in Regenerative Medicine: An Updated Review. Pharmaceutics 2023, 15, 695. [Google Scholar] [CrossRef]
- Harrison, P.M. The structure and function of ferritin. Biochem. Educ. 1986, 14, 154–162. [Google Scholar] [CrossRef]
- Montemiglio, L.C.; Testi, C.; Ceci, P.; Falvo, E.; Pitea, M.; Savino, C.; Arcovito, A.; Peruzzi, G.; Baiocco, P.; Mancia, F.; et al. Cryo-EM structure of the human ferritin–transferrin receptor 1 complex. Nat. Commun. 2019, 10, 1121. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Turris, V.; Cardoso Trabuco, M.; Peruzzi, G.; Boffi, A.; Testi, C.; Vallone, B.; Celeste Montemiglio, L.; Georges, A.D.; Calisti, L.; Benni, I.; et al. Humanized archaeal ferritin as a tool for cell targeted delivery. Nanoscale 2017, 9, 647–655. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Incocciati, A.; Bertuccini, L.; Boffi, A.; Macone, A.; Bonamore, A. Unlocking the Treasure Box: The Role of HEPES Buffer in Disassembling an Uncommon Ferritin Nanoparticle. Separations 2022, 9, 222. [Google Scholar] [CrossRef]
- Lee, N.K.; Cho, S.; Kim, I.-S. Ferritin—A multifaceted protein scaffold for biotherapeutics. Exp. Mol. Med. 2022, 54, 1652–1657. [Google Scholar] [CrossRef] [PubMed]
- Palombarini, F.; Di Fabio, E.; Boffi, A.; Macone, A.; Bonamore, A. Ferritin Nanocages for Protein Delivery to Tumor Cells. Molecules 2020, 25, 825. [Google Scholar] [CrossRef] [Green Version]
- Macone, A.; Masciarelli, S.; Palombarini, F.; Quaglio, D.; Boffi, A.; Trabuco, M.C.; Baiocco, P.; Fazi, F.; Bonamore, A. Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells. Sci. Rep. 2019, 9, 11749. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Palombarini, F.; Masciarelli, S.; Incocciati, A.; Liccardo, F.; Di Fabio, E.; Iazzetti, A.; Fabrizi, G.; Fazi, F.; Macone, A.; Bonamore, A.; et al. Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells. J. Nanobiotechnol. 2021, 19, 172. [Google Scholar] [CrossRef] [PubMed]
- Calisti, L.; Trabuco, M.C.; Boffi, A.; Testi, C.; Montemiglio, L.C.; des Georges, A.; Benni, I.; Ilari, A.; Taciak, B.; Białasek, M.; et al. Engineered ferritin for lanthanide binding. PLoS ONE 2018, 13, e0201859. [Google Scholar] [CrossRef] [Green Version]
- Sana, B.; Johnson, E.; Le Magueres, P.; Criswell, A.; Cascio, D.; Lim, S. The role of nonconserved residues of Archaeoglobus fulgidus ferritin on its unique structure and biophysical properties. J. Biol. Chem. 2013, 288, 32663. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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MDPI and ACS Style
Incocciati, A.; Cappelletti, C.; Boffi, A.; Macone, A.; Bonamore, A. Harnessing Buffer Solutions to Modify the Association State of Ferritin Nanoparticles. Separations 2023, 10, 414. https://doi.org/10.3390/separations10070414
AMA Style
Incocciati A, Cappelletti C, Boffi A, Macone A, Bonamore A. Harnessing Buffer Solutions to Modify the Association State of Ferritin Nanoparticles. Separations. 2023; 10(7):414. https://doi.org/10.3390/separations10070414
Chicago/Turabian StyleIncocciati, Alessio, Chiara Cappelletti, Alberto Boffi, Alberto Macone, and Alessandra Bonamore. 2023. "Harnessing Buffer Solutions to Modify the Association State of Ferritin Nanoparticles" Separations 10, no. 7: 414. https://doi.org/10.3390/separations10070414
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