Hydrophobicity-enhanced ferritin nanoparticles for efficient encapsulation and targeted delivery of hydrophobic drugs to tumor cells
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články
Grantová podpora
PNRR M4C2-Investimento 1.4-CN00000041
NextGenerationEU
SP1221846100319C
Sapienza University of Rome, SEED-PNR 2022
SVV260664
Charles University
PubMed
37883077
PubMed Central
PMC10661074
DOI
10.1002/pro.4819
Knihovny.cz E-zdroje
- Klíčová slova
- doxorubicin, drug delivery, ellipticine, ferritin, hydrophobic drugs, nanoparticle, protein engineering, tumor cells,
- MeSH
- antitumorózní látky * farmakologie chemie MeSH
- apoferritiny genetika MeSH
- doxorubicin farmakologie chemie MeSH
- elipticiny * MeSH
- ferritin genetika chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- systémy cílené aplikace léků MeSH
- tryptofan MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky * MeSH
- apoferritiny MeSH
- doxorubicin MeSH
- elipticiny * MeSH
- ferritin MeSH
- nosiče léků MeSH
- tryptofan MeSH
Ferritin, a naturally occurring iron storage protein, has gained significant attention as a drug delivery platform due to its inherent biocompatibility and capacity to encapsulate therapeutic agents. In this study, we successfully genetically engineered human H ferritin by incorporating 4 or 6 tryptophan residues per subunit, strategically oriented towards the inner cavity of the nanoparticle. This modification aimed to enhance the encapsulation of hydrophobic drugs into the ferritin cage. Comprehensive characterization of the mutants revealed that only the variant carrying four tryptophan substitutions per subunit retained the ability to disassemble and reassemble properly. As a proof of concept, we evaluated the loading capacity of this mutant with ellipticine, a natural hydrophobic indole alkaloid with multimodal anticancer activity. Our data demonstrated that this specific mutant exhibited significantly higher efficiency in loading ellipticine compared to human H ferritin. Furthermore, to evaluate the versatility of this hydrophobicity-enhanced ferritin nanoparticle as a drug carrier, we conducted a comparative study by also encapsulating doxorubicin, a commonly used anticancer drug. Subsequently, we tested both ellipticine and doxorubicin-loaded nanoparticles on a promyelocytic leukemia cell line, demonstrating efficient uptake by these cells and resulting in the expected cytotoxic effect.
Center of Life Nano and Neuro Science Italian Institute of Technology Rome Italy
Core Facilities Istituto Superiore di Sanità Rome Italy
Department of Biochemical Sciences A Rossi Fanelli Sapienza University of Rome Rome Italy
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Abdelkhaliq A, van der Zande M, Punt A, Helsdingen R, Boeren S, Vervoort JJM, et al. Impact of nanoparticle surface functionalization on the protein corona and cellular adhesion, uptake and transport. J Nanobiotechnol. 2018;16:70. 10.1186/s12951-018-0394-6 PubMed DOI PMC
Abdulwahid FS, Haider AJ, Al‐Musawi S. Folate decorated dextran‐coated magnetic nanoparticles for targeted delivery of ellipticine in cervical cancer cells. Adv Nat Sci Nanosci Nanotechnol. 2023;14:15001. 10.1088/2043-6262/aca606 DOI
Bellini M, Mazzucchelli S, Galbiati E, Sommaruga S, Fiandra L, Truffi M, et al. Protein nanocages for self‐triggered nuclear delivery of DNA‐targeted chemotherapeutics in cancer cells. J Control Release. 2014;196:184–196. 10.1016/j.jconrel.2014.10.002 PubMed DOI
Blazkova I, Nguyen HV, Dostalova S, Kopel P, Stanisavljevic M, Vaculovicova M, et al. Apoferritin modified magnetic particles as doxorubicin carriers for anticancer drug delivery. Int J Mol Sci. 2013;14(7):13391–13402. 10.3390/ijms140713391 PubMed DOI PMC
Boisguérin P, Konate K, Josse E, Vivès E, Deshayes S. Peptide‐based nanoparticles for therapeutic nucleic acid delivery. Biomedicine. 2021;9(5):583. 10.3390/biomedicines9050583 PubMed DOI PMC
Calisti L, Trabuco MC, Boffi A, Testi C, Montemiglio LC, des Georges A, et al. Engineered ferritin for lanthanide binding. PLoS One. 2018;13:e0201859. 10.1371/journal.pone.0201859 PubMed DOI PMC
Dan VM, Varghese TS, Viswanathan G, Baby S. Ellipticine, its derivatives: re‐evaluation of clinical suitability with the aid of drug delivery systems. Curr Cancer Drug Targets. 2020;20(1):33–46. 10.2174/1568009619666190927150131 PubMed DOI
Daniels TR, Bernabeu E, Rodríguez JA, Patel S, Kozman M, Chiappetta DA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. BBA ‐ General Subjects. 2012;1820(3):291–317. 10.1016/j.bbagen.2011.07.016 PubMed DOI PMC
Falvo E, Damiani V, Conti G, Boschi F, Messana K, Giacomini P, et al. High activity and low toxicity of a novel CD71‐targeting nanotherapeutic named The‐0504 on preclinical models of several human aggressive tumors. J Exp Clin Cancer Res. 2021;40(1):63. 10.1186/s13046-021-01851-8 PubMed DOI PMC
Falvo E, Tremante E, Arcovito A, Papi M, Elad N, Boffi A, et al. Improved doxorubicin encapsulation and pharmacokinetics of ferritin–fusion protein nanocarriers bearing proline, serine, and alanine elements. Biomacromolecules. 2016;17(2):514–522. 10.1021/acs.biomac.5b01446 PubMed DOI
Freskgaard PO, Maartensson LG, Jonasson P, Jonsson BH, Carlsson U. Assignment of the contribution of the tryptophan residues to the circular dichroism spectrum of human carbonic anhydrase II. Biochemistry. 1994;33(47):14281–14288. 10.1021/bi00251a041 PubMed DOI
Habibi N, Mauser A, Ko Y, Lahann J. Protein nanoparticles: uniting the power of proteins with engineering design approaches. Adv Sci. 2022;9(8):2104012. 10.1002/advs.202104012 PubMed DOI PMC
He J, Fan K, Yan X. Ferritin drug carrier (FDC) for tumor targeting therapy. JCR. 2019;311–312:288–300. 10.1016/j.jconrel.2019.09.002 PubMed DOI
Hong S, Choi DW, Kim HN, Park CG, Lee W, Park HH. Protein‐based nanoparticles as drug delivery systems. Pharmaceutics. 2020;12(7):604. 10.3390/pharmaceutics12070604 PubMed DOI PMC
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(8):222. 10.3390/separations9080222 DOI
Inoue I, Chiba M, Ito K, Okamatsu Y, Suga Y, Kitahara Y, et al. One‐step construction of ferritin encapsulation drugs for cancer chemotherapy. Nanoscale. 2021;13(3):1875–1883. 10.1039/d0nr04019c PubMed DOI
Jiang B, Chen X, Sun G, Chen X, Yin Y, Jin Y, et al. A natural drug entry channel in the ferritin nanocage. Nano Today. 2020;35:100948. 10.1016/j.nantod.2020.100948 DOI
Kianfar E. Protein nanoparticles in drug delivery: animal protein, plant proteins and protein cages, albumin nanoparticles. J Nanobiotechnol. 2021;19:159. 10.1186/s12951-021-00896-3 PubMed DOI PMC
Kim M, Rho Y, Jin KS, Ahn B, Jung S, Kim H, et al. pH‐dependent structures of ferritin and apoferritin in solution: disassembly and reassembly. Biomacromolecules. 2011;12(5):1629–1640. 10.1021/bm200026v PubMed DOI
Li L, Muñoz‐Culla M, Carmona U, Lopez MP, Yang F, Trigueros C, et al. Ferritin‐mediated siRNA delivery and gene silencing in human tumor and primary cells. Biomaterials. 2016;98:143–151. 10.1016/j.biomaterials.2016.05.006 PubMed DOI
Liang M, Fan K, Zhou M, Duan D, Zheng J, Yang D, et al. H‐ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single‐dose injection. Proc Natl Acad Sci. 2014;111(41):14900–14905. 10.1073/pnas.1407808111 PubMed DOI PMC
Liu J, Xiao Y, Allen C. Polymer–drug compatibility: a guide to the development of delivery systems for the anticancer agent, ellipticine. J Pharm Sci. 2004;93(1):132–143. 10.1002/jps.10533 PubMed DOI
Lyonsa VJ, Pappas D. Affinity separation and subsequent terminal differentiation of acute myeloid leukemia cells using the human transferrin receptor (CD71) as a capture target. Analyst. 2019;144:3369–3380. 10.1039/C8AN02357C PubMed DOI
Macone A, Masciarelli S, Palombarini F, Quaglio D, Boffi A, Trabuco MC, et al. Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells. Sci Rep. 2019;9:11749. 10.1038/s41598-019-48037-z PubMed DOI PMC
Mazzucchelli S, Truffi M, Baccarini F, Beretta M, Sorrentino L, Bellini M, et al. H‐ferritin‐nanocaged olaparib: a promising choice for both BRCA‐mutated and sporadic triple negative breast cancer. Sci Rep. 2017;7:7505. 10.1038/s41598-017-07617-7 PubMed DOI PMC
Miao Y, Yang T, Yang S, Mao C. Protein nanoparticles directed cancer imaging and therapy. Nano Convergence. 2022;9:2. 10.1186/s40580-021-00293-4 PubMed DOI PMC
Millera CM, McCarthy FO. Isolation, biological activity and synthesis of the natural product ellipticine and related pyridocarbazoles. RSC Adv. 2012;2:8883–8918. 10.1039/C2RA20584J DOI
Mohanty A, Mithra K, Jena SS, Behera RK. Kinetics of ferritin self‐assembly by laser light scattering: impact of subunit concentration, pH, and ionic strength. Biomacromolecules. 2021;22(4):1389–1398. 10.1021/acs.biomac.0c01562 PubMed DOI
Ning C, Dong Y, Yang K, Li X, Wang F, Zhang Y. Co‐encapsulation of hydrophilic and hydrophobic drugs into human H chain ferritin nanocarrier enhances antitumor efficacy. ACS Biomater Sci Eng. 2023;9(5):2572–2583. 10.1021/acsbiomaterials.3c00218 PubMed DOI
Olshefsky A, Richardson C, Pun SH, King NP. Engineering self‐assembling protein nanoparticles for therapeutic delivery. Bioconjug Chem. 2022;33(11):2018–2034. 10.1021/acs.bioconjchem.2c00030 PubMed DOI PMC
Palombarini F, Di Fabio E, Boffi A, Macone A, Bonamore A. Ferritin nanocages for protein delivery to tumor cells. Molecules. 2020;25(4):825. 10.3390/molecules25040825 PubMed DOI PMC
Palombarini F, Masciarelli S, Incocciati A, Liccardo F, Di Fabio E, Iazzetti A, et al. Self‐assembling ferritin‐dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells. J Nanobiotechnol. 2021;19:172. 10.1186/s12951-021-00921-5 PubMed DOI PMC
Segel M, Blake Lash B, Song J, Ladha A, Liu CC, Jin X, et al. Mammalian retrovirus‐like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery. Science. 2021;373:882–889. 10.1126/science.abg6155 PubMed DOI PMC
Semisotnov GV, Rodionova NA, Razgulyaev OI, Uversky VN, Gripas AF, Gilmanshin RI. Study of the “molten globule” intermediate state in protein folding by a hydrophobic fluorescent probe. Biopolymers. 1991;31(1):119–128. 10.1002/bip.360310111 PubMed DOI
Song N, Zhang J, Zhai J, Hong J, Yuan C, Liang M. Ferritin: a multifunctional Nanoplatform for biological detection, imaging diagnosis, and drug delivery. Acc Chem Res. 2021;54(17):3313–3325. 10.1021/acs.accounts.1c00267 PubMed DOI
Spicer CD, Jumeaux C, Gupta B, Stevens MM. Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications. Chem Soc Rev. 2018;47:3574–3620. 10.1039/C7CS00877E PubMed DOI PMC
Stiborová M, Rupertová M, Frei E. Cytochrome P450‐ and peroxidase‐mediated oxidation of anticancer alkaloid ellipticine dictates its anti‐tumor efficiency. Biochem Biophys Acta Proteins Proteomics. 2011;1814(1):175–185. 10.1016/j.bbapap.2010.05.016 PubMed DOI
Stryer L. The interaction of a naphthalene dye with apomyoglobin and apohemoglobin: a fluorescent probe of non‐polar binding sites. J Mol Biol. 1965;13(2):482–495. 10.1016/S0022-2836(65)80111-5 PubMed DOI
Studenovský M, Sedláček O, Hrubý M, Pánek J, Ulbrich K. Multi‐responsive polymer micelles as ellipticine delivery carriers for cancer therapy. Anticancer Res. 2015;35(2):753–757. PubMed
Sun X, Hong Y, Gong Y, Zheng S, Xie D. Bioengineered ferritin nanocarriers for cancer therapy. Int J Mol Sci. 2021;22(13):7023. 10.3390/ijms22137023 PubMed DOI PMC
Tesarova B, Dostalova S, Smidova V, Goliasova Z, Skubalova Z, Michalkova H, et al. Surface‐PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine. Appl Mater Today. 2020;18:100501. 10.1016/j.apmt.2019.100501 DOI
Wang Z, Zhao Y, Zhang S, Chen X, Sun G, Zhang B, et al. Re‐engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy. Theranostics. 2022;12(4):1800–1815. 10.7150/thno.68459 PubMed DOI PMC
Wu X, Jiao Z, Zhang J, Li F, Li Y. Expression of TFRC helps to improve the antineoplastic effect of Ara‐C on AML cells through a targeted delivery carrier. J Nanobiotechnol. 2023;21:126. 10.1186/s12951-023-01881-8 PubMed DOI PMC
Wu Y, Sadatmousavi P, Wang R, Lu S, Yuan YF, Chen P. Self‐assembling peptide‐based nanoparticles enhance anticancer effect of ellipticine in vitro and in vivo. Int J Nanomed. 2012;7:3221–3231. 10.2147/IJN.S31858 PubMed DOI PMC
Wu M, Ye Z, Liu Y, Liu B, Zhao X. Release of hydrophobic anticancer drug from a newly designed self‐assembling peptide. Mol Biosyst. 2011;7:2040–2047. 10.1039/C0MB00271B PubMed DOI
Yin S, Davey K, Dai S, Liu Y, Bi J. A critical review of ferritin as a drug nanocarrier: structure, properties, comparative advantages and challenges. Particuology. 2022;64:65–84. 10.1016/j.partic.2021.04.020 DOI
Zhang S, Li Y, Bao Z, Sun N, Lin S. Internal cavity amplification of shell‐like ferritin regulated with the change of the secondary and tertiary structure induced by PEF technology. Int J Biol Macromol. 2021;182:849–857. 10.1016/j.ijbiomac.2021.04.072 PubMed DOI
Zhu Y, Zhu Y, Cao T, Liu X, Liu X, Yan Y, et al. Ferritin‐based nanomedicine for disease treatment. Med Rev. 2023;3(1):49–74. 10.1515/mr-2023-0001 PubMed DOI PMC