Applications of ferritin-based delivery system in biomedical field
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摘要:
铁蛋白普遍存在于各种生物体内,负责储存过量铁以维持体内铁平衡。由于铁蛋白具有固有靶向性、天然空腔结构、可逆性自组装、高生物相容性及易被修饰等天然优势,被认为是一种理想的递送系统,广泛应用于多个领域。本文重点综述铁蛋白的生物学特性、功能化修饰、载药策略以及在药物递送、生物催化、光动力治疗、医学成像以及疫苗研究等生物医学领域中的研究进展和应用前景,为基于铁蛋白的递送系统在生物医学领域中的相关研究提供借鉴。
Abstract:Ferritin is widely present in various organisms and is responsible for storing excess iron to maintain iron balance in vivo. Due to its inherent targeting ability, natural cavity structure, reversible self-assembly, high biocompatibility, and easy modification, ferritin is considered to be an ideal delivery system, which is widely used in many fields. This review summarizes the biological characteristics, functionalization, drug loading strategies, research progress and application prospects of ferritin-based nanocarrier systems in biomedical fields, such as drug delivery, biocatalysis, photodynamic therapy, medical imaging and vaccine research, aiming to provide some reference for related biomedical research based on ferritin delivery systems.
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表 1 以铁蛋白作为递送系统的生物医学研究
领域 包载药物/表面修饰 铁蛋白类型 载药方法 功能应用 参考文献 药物载体 雷帕霉素和Erastin 铁蛋白 物理孵育 诱导肿瘤细胞铁死亡 [29] 光敏剂和表柔比星 马脾脏去铁蛋白 pH解聚/重组装 清除乳腺癌转移的CSCs [28] 阿霉素 热球菌铁蛋白 尿毒梯度 抑制肝癌生长及肺转移 [21] 核酸递送 siRNA 人去铁蛋白 pH解聚/重组装 免疫激活及抗炎 [35] siRNA 人重链铁蛋白 pH解聚/重组装 干扰RNA表达并抑制肿瘤生长 [36] TLR核酸配体 人铁蛋白突变体 pH解聚/重组装 抗肿瘤免疫治疗 [12] 多肽类药物 吞噬诱导肽SIRPα 铁蛋白 基因工程 肿瘤靶向治疗 [37] 多价凝块靶向肽 溶血栓铁蛋白 基因工程 靶向破坏血管中血栓 [38] 血管紧张素转换酶抑制肽 马脾脏铁蛋白 物理孵育 肠道靶向释放 [39] 生物催化 Fe3O4 人重链铁蛋白 温度通道 过氧化氢酶活性 [42] Co3O4 激烈火球菌铁蛋白 原位氧化 类过氧化物酶活性 [43] 光动力治疗 ZnF16Pc RGD修饰的铁蛋白 物理孵育 PDT治疗肿瘤 [47] ZnF16Pc FAP修饰的铁蛋白 pH解聚/重组装 选择性清除肿瘤部位CAF [48] 生物成像 68Ga 68Ga-NOTA-Tf 物理孵育 核成像 [51] 99mTc 人重链铁蛋白 物理孵育 SPECT和CT双模式成像 [52] IR820 铁蛋白 pH解聚/重组装 光声/荧光多模式成像 [54] 疫苗研发 SARs-CoV-2抗原 幽门螺杆菌铁蛋白 基因工程 SARs-CoV-2铁蛋白纳米疫苗 [57] SpyTag抗原 铁蛋白 点击连接 肿瘤个性化疫苗 [59] 甲型流感血凝素 幽门螺杆菌铁蛋白 基因工程 流感疫苗 [60] -
[1] V Laufberger. Sur la cristallisation de la ferritine[J]. Soc Chim Biol, 1937, 19: 1575-1582.
[2] Jiang B, Fang L, Wu KM, et al. Ferritins as natural and artificial nanozymes for theranostics[J]. Theranostics, 2020, 10(2): 687-706. doi: 10.7150/thno.39827
[3] Truffi M, Fiandra L, Sorrentino L, et al. Ferritin nanocages: a biological platform for drug delivery, imaging and theranostics in cancer[J]. Pharmacol Res, 2016, 107: 57-65. doi: 10.1016/j.phrs.2016.03.002
[4] Yin S, Davey K, Dai S, et al. A critical review of ferritin as a drug nanocarrier: structure, properties, comparative advantages and challenges[J]. Particuology, 2022, 64: 65-84. doi: 10.1016/j.partic.2021.04.020
[5] Levi S, Yewdall SJ, Harrison PM, et al. Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin[J]. Biochem J, 1992, 288 (Pt 2): 591-596.
[6] Pediconi N, Ghirga F, Del Plato C, et al. Design and synthesis of piperazine-based compounds conjugated to humanized ferritin as delivery system of siRNA in cancer cells[J]. Bioconjug Chem, 2021, 32(6): 1105-1116. doi: 10.1021/acs.bioconjchem.1c00137
[7] Zhang JL, Cheng DF, He JY, et al. Cargo loading within ferritin nanocages in preparation for tumor-targeted delivery[J]. Nat Protoc, 2021, 16(10): 4878-4896. doi: 10.1038/s41596-021-00602-5
[8] Li L, Fang CJ, Ryan JC, et al. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1[J]. Proc Natl Acad Sci U S A, 2010, 107(8): 3505-3510. doi: 10.1073/pnas.0913192107
[9] Meng DM, Zhu L, Zhang LQ, et al. Succinylated ferritin as a novel nanocage-like vehicle of polyphenol: structure, stability, and absorption analysis[J]. Food Chem, 2021, 361: 130069. doi: 10.1016/j.foodchem.2021.130069
[10] Zhen ZP, Tang W, Chen HM, et al. RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors[J]. ACS Nano, 2013, 7(6): 4830-4837. doi: 10.1021/nn305791q
[11] Fang L, Zhang RF, Shi L, et al. Protein-nanocaged selenium induces t(8;21) leukemia cell differentiation via epigenetic regulation[J]. Adv Sci, 2023, 10(35): e2300698. doi: 10.1002/advs.202300698
[12] Zhang BL, Chen XH, Tang GH, et al. Constructing a nanocage-based universal carrier for delivering TLR-activating nucleic acids to enhance antitumor immunotherapy[J]. Nano Today, 2022, 46: 101564. doi: 10.1016/j.nantod.2022.101564
[13] Xin Q, Wang DJ, Wang SH, et al. Tackling esophageal squamous cell carcinoma with ITFn-Pt(IV): a novel fusion of PD-L1 blockade, chemotherapy, and T-cell activation[J]. Adv Healthc Mater, 2024, 13(11): e2303623. doi: 10.1002/adhm.202303623
[14] Liang MM, Fan KL, Zhou M, et al. H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection[J]. Proc Natl Acad Sci U S A, 2014, 111(41): 14900-14905. doi: 10.1073/pnas.1407808111
[15] Yao HC, Guo XF, Zhou HJ, et al. Mild acid-responsive “nanoenzyme capsule” remodeling of the tumor microenvironment to increase tumor penetration[J]. ACS Appl Mater Interfaces, 2020, 12(18): 20214-20227. doi: 10.1021/acsami.0c03022
[16] Wang ZR, Zhang S, Zhang RF, et al. Bioengineered dual-targeting protein nanocage for stereoscopical loading of synergistic hydrophilic/hydrophobic drugs to enhance anticancer efficacy[J]. Adv Funct Materials, 2021, 31(29): 2102004. doi: 10.1002/adfm.202102004
[17] Ahn B, Lee SG, Yoon HR, et al. Four-fold channel-nicked human ferritin nanocages for active drug loading and pH-responsive drug release[J]. Angew Chem Int Ed, 2018, 57(11): 2909-2913. doi: 10.1002/anie.201800516
[18] Li ZP, Maity B, Hishikawa Y, et al. Importance of the subunit-subunit interface in ferritin disassembly: a molecular dynamics study[J]. Langmuir, 2022, 38(3): 1106-1113. doi: 10.1021/acs.langmuir.1c02753
[19] Xia XY, Tan XY, Wu C, et al. PM1-loaded recombinant human H-ferritin nanocages: a novel pH-responsive sensing platform for the identification of cancer cells[J]. Int J Biol Macromol, 2022, 199: 223-233. doi: 10.1016/j.ijbiomac.2021.12.068
[20] Conti L, Ciambellotti S, Giacomazzo GE, et al. Ferritin nanocomposites for the selective delivery of photosensitizing ruthenium-polypyridyl compounds to cancer cells[J]. Inorg Chem Front, 2022, 9(6): 1070-1081. doi: 10.1039/D1QI01268A
[21] Jiang B, Zhang RF, Zhang JL, et al. GRP78-targeted ferritin nanocaged ultra-high dose of doxorubicin for hepatocellular carcinoma therapy[J]. Theranostics, 2019, 9(8): 2167-2182. doi: 10.7150/thno.30867
[22] Yang R, Liu YQ, Meng DM, et al. Urea-driven epigallocatechin gallate (EGCG) permeation into the ferritin cage, an innovative method for fabrication of protein-polyphenol co-assemblies[J]. J Agric Food Chem, 2017, 65(7): 1410-1419. doi: 10.1021/acs.jafc.6b04671
[23] McHugh CA, Fontana J, Nemecek D, et al. A virus capsid-like nanocompartment that stores iron and protects bacteria from oxidative stress[J]. EMBO J, 2014, 33(17): 1896-1911. doi: 10.15252/embj.201488566
[24] Yang R, Tian J, Liu YQ, et al. Thermally induced encapsulation of food nutrients into phytoferritin through the flexible channels without additives[J]. J Agric Food Chem, 2017, 65(46): 9950-9955. doi: 10.1021/acs.jafc.7b03949
[25] Xia HN, Xu HT, Wang JR, et al. Heat sensitive E-helix cut ferritin nanocages for facile and high-efficiency loading of doxorubicin[J]. Int J Biol Macromol, 2023, 253: 126973. doi: 10.1016/j.ijbiomac.2023.126973
[26] Jiang B, Chen XH, Sun GM, et al. A natural drug entry channel in the ferritin nanocage[J]. Nano Today, 2020, 35: 100948. doi: 10.1016/j.nantod.2020.100948
[27] Pang J, Feng X, Liang Q, et al. Ferritin-nanocaged ATP traverses the blood-testis barrier and enhances sperm motility in an asthenozoospermia model[J]. ACS Nano, 2022, 16(3): 4175-4185. doi: 10.1021/acsnano.1c10029
[28] Tan T, Wang H, Cao HQ, et al. Deep tumor-penetrated nanocages improve accessibility to cancer stem cells for photothermal-chemotherapy of breast cancer metastasis[J]. Adv Sci, 2018, 5(12): 1801012. doi: 10.1002/advs.201801012
[29] Li YQ, Wang XY, Yan JJ, et al. Nanoparticle ferritin-bound erastin and rapamycin: a nanodrug combining autophagy and ferroptosis for anticancer therapy[J]. Biomater Sci, 2019, 7(9): 3779-3787. doi: 10.1039/C9BM00653B
[30] Liu R, Liang Q, Luo JQ, et al. Ferritin-based nanocomposite hydrogel promotes tumor penetration and enhances cancer chemoimmunotherapy[J]. Adv Sci, 2024, 11(3): e2305217. doi: 10.1002/advs.202305217
[31] Wang CL, Zhang W, He YJ, et al. Ferritin-based targeted delivery of arsenic to diverse leukaemia types confers strong anti-leukaemia therapeutic effects[J]. Nat Nanotechnol, 2021, 16(12): 1413-1423. doi: 10.1038/s41565-021-00980-7
[32] Wang ZR, Zhao Y, Zhang S, et al. Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy[J]. Theranostics, 2022, 12(4): 1800-1815. doi: 10.7150/thno.68459
[33] Hald Albertsen C, Kulkarni JA, Witzigmann D, et al. The role of lipid components in lipid nanoparticles for vaccines and gene therapy[J]. Adv Drug Deliv Rev, 2022, 188: 114416. doi: 10.1016/j.addr.2022.114416
[34] Zimmermann CM, Baldassi D, Chan KR, et al. Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery[J]. J Control Release, 2022, 351: 137-150. doi: 10.1016/j.jconrel.2022.09.021
[35] Li L, Muñoz-Culla M, Carmona U, et al. Ferritin-mediated si-RNA delivery and gene silencing in human tumor and primary cells[J]. Biomaterials, 2016, 98: 143-151. doi: 10.1016/j.biomaterials.2016.05.006
[36] Huang HQ, Yuan SR, Ma Z, et al. Genetic recombination of poly(l-lysine) functionalized apoferritin nanocages that resemble viral capsid nanometer-sized platforms for gene therapy[J]. Biomater Sci, 2020, 8(6): 1759-1770. doi: 10.1039/C9BM01822K
[37] Lee EJ, Nam GH, Lee NK, et al. Nanocage-therapeutics prevailing phagocytosis and immunogenic cell death awakens immunity against cancer[J]. Adv Mater, 2018, 30(10): 1705581. doi: 10.1002/adma.201705581
[38] Seo J, Al-Hilal TA, Jee JG, et al. A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots[J]. Nanomed-Nanotechnol Biol Med, 2018, 14(3): 633-642. doi: 10.1016/j.nano.2017.12.022
[39] Li Y, Zhang YC, Chai Z, et al. Entrapment of an ACE inhibitory peptide into ferritin nanoparticles coated with sodium deoxycholate: improved chemical stability and intestinal absorption[J]. LWT, 2021, 147: 111547. doi: 10.1016/j.lwt.2021.111547
[40] Wu J, Wang XY, Wang Q, et al. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II)[J]. Chem Soc Rev, 2019, 48(4): 1004-1076. doi: 10.1039/C8CS00457A
[41] Wang CY, Liu QQ, Huang XL, et al. Ferritin nanocages: a versatile platform for nanozyme design[J]. J Mater Chem B, 2023, 11(19): 4153-4170. doi: 10.1039/D3TB00192J
[42] Zhao S, Duan HX, Yang YL, et al. Fenozyme protects the integrity of the blood-brain barrier against experimental cerebral malaria[J]. Nano Lett, 2019, 19(12): 8887-8895. doi: 10.1021/acs.nanolett.9b03774
[43] Jiang B, Yan L, Zhang JL, et al. Biomineralization synthesis of the cobalt nanozyme in SP94-ferritin nanocages for prognostic diagnosis of hepatocellular carcinoma[J]. ACS Appl Mater Interfaces, 2019, 11(10): 9747-9755. doi: 10.1021/acsami.8b20942
[44] Wu J, Wei YH, Lan JP, et al. Screening of protein-based ultrasmall nanozymes for building cell-mimicking catalytic vesicles[J]. Small, 2022, 18(39): e2202145. doi: 10.1002/smll.202202145
[45] Zeng RQ, Chang XX, Zhang T, et al. Simultaneous integration of the photosensitizer hemin and biocatalyst nanoferrihydrite into a single protein nanocage for selectively photocatalytic CO2 reduction[J]. Appl Catal B Environ, 2024, 343: 123521. doi: 10.1016/j.apcatb.2023.123521
[46] Osuchowski M, Bartusik-Aebisher D, Osuchowski F, et al. Photodynamic therapy for prostate cancer - A narrative review[J]. Photodiagnosis Photodyn Ther, 2021, 33: 102158. doi: 10.1016/j.pdpdt.2020.102158
[47] Zhen ZP, Tang W, Guo CL, et al. Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer[J]. ACS Nano, 2013, 7(8): 6988-6996. doi: 10.1021/nn402199g
[48] Zhou SY, Zhen ZP, Paschall AV, et al. FAP-targeted photodynamic therapy mediated by ferritin nanoparticles elicits an immune response against cancer cells and cancer associated fibroblasts[J]. Adv Funct Mater, 2021, 31(7): 2007017. doi: 10.1002/adfm.202007017
[49] Wang CL, Wang XJ, Zhang W, et al. Shielding ferritin with a biomineralized shell enables efficient modulation of tumor microenvironment and targeted delivery of diverse therapeutic agents[J]. Adv Mater, 2022, 34(5): e2107150. doi: 10.1002/adma.202107150
[50] Wu SY, Ye YX, Zhang Q, et al. Multifunctional protein hybrid nanoplatform for synergetic photodynamic-chemotherapy of malignant carcinoma by homologous targeting combined with oxygen transport[J]. Adv Sci, 2023, 10(5): e2203742. doi: 10.1002/advs.202203742
[51] Shibata Y, Yasui H, Higashikawa K, et al. Transferrin-based radiolabeled probe predicts the sensitivity of human renal cancer cell lines to ferroptosis inducer erastin[J]. Biochem Biophys Rep, 2021, 26: 100957.
[52] Liang MM, Tan H, Zhou J, et al. Bioengineered H-ferritin nanocages for quantitative imaging of vulnerable plaques in atherosclerosis[J]. ACS Nano, 2018, 12(9): 9300-9308. doi: 10.1021/acsnano.8b04158
[53] Zhang QH, Chen JW, Shen J, et al. Inlaying radiosensitizer onto the polypeptide shell of drug-loaded ferritin for imaging and combinational chemo-radiotherapy[J]. Theranostics, 2019, 9(10): 2779-2790. doi: 10.7150/thno.33472
[54] Huang P, Rong PF, Jin A, et al. Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy[J]. Adv Mater, 2014, 26(37): 6401-6408. doi: 10.1002/adma.201400914
[55] Kanekiyo M, Joyce MG, Gillespie RA, et al. Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses[J]. Nat Immunol, 2019, 20(3): 362-372. doi: 10.1038/s41590-018-0305-x
[56] Ma XC, Zou F, Yu F, et al. Nanoparticle vaccines based on the receptor binding domain (RBD) and heptad repeat (HR) of SARS-CoV-2 elicit robust protective immune responses[J]. Immunity, 2020, 53 (6): 1315-1330. e9.
[57] Joyce MG, Chen WH, Sankhala RS, et al. SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity[J]. Cell Rep, 2021, 37(12): 110143. doi: 10.1016/j.celrep.2021.110143
[58] Qiao YB, Li S, Jin SH, et al. A self-assembling nanoparticle vaccine targeting the conserved epitope of influenza virus hemagglutinin stem elicits a cross-protective immune response[J]. Nanoscale, 2022, 14(8): 3250-3260. doi: 10.1039/D1NR08460G
[59] Wang WJ, Liu ZD, Zhou XX, et al. Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy[J]. Nanomed-Nanotechnol Biol Med, 2019, 16: 69-78. doi: 10.1016/j.nano.2018.11.009
[60] Houser KV, Chen GL, Carter C, et al. Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial[J]. Nat Med, 2022, 28(2): 383-391. doi: 10.1038/s41591-021-01660-8