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纳米载体具有独特的物理、化学和生物特性,为克服癌症成像、诊断和治疗领域的困难提供了有效途径。核素标记的纳米载体用于活体示踪、核素治疗及预后监测等已成为放射化学和核医学领域中的研究趋势[1-2]。纳米载体与放射性核素的结合在改善当前的癌症核素诊断和治疗方面具有巨大潜力[3-4]。然而,放射性核素与纳米载体之间的相互作用、载体表面化学修饰水平等会影响纳米载体的药代动力学和药效学特性。因此,每一种放射性标记方法都需要仔细处理多种因素的影响,这些苛刻的要求促使研究人员为纳米载体的放射性标记不断开发不同的创新解决方案。根据标记过程中是否使用螯合剂将标记策略分为有螯合剂和无螯合剂两大类。(1)有螯合剂:使用螯合剂通过配位标记放射性核素,有直接标记和预标记两种方法。(2)无螯合剂:简单有效的无螯合剂标记方法能够保持纳米材料本身的特性并减少反应步骤,目前常用的策略有吸附法、掺杂法、中子质子激活法、标记佐剂法等。笔者旨在综述现有放射性核素标记纳米载体的不同策略的研究进展。
纳米载体的放射性核素标记方法研究进展
Progress in radionuclide labeling methods for nanocarriers
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摘要: 基于纳米医学策略改善放射性核素递送效率、提高获取病灶信息的灵敏度和肿瘤治疗疗效已成为当今研究的热点。虽然不同类型的纳米载体已被用作放射性示踪剂,但放射性标记仍然是一个关键步骤。为确保放射性核素标记的标记率和稳定性,根据纳米载体类型、放射性核素和反应条件选取最合适的放射性标记策略是至关重要的。笔者主要综述了目前有螯合剂和无螯合剂两大类放射性核素的标记策略及其优缺点,以期为放射性核素标记不同纳米载体进行核素诊疗提供帮助。Abstract: Improving the delivery efficiency of radioactive nuclides, increasing the sensitivity of obtaining lesion information, and enhancing the efficacy of tumor treatment based on nanomedicine strategies have become a hot research topic today. Different types of nanocarriers have been used as radioactive tracer, but radioactive labeling is still a key step. To ensure the labeling rate and stability of radionuclide-labeled nanocarriers, the most appropriate radiolabeling strategies are selected on the basis of the type of materials, radionuclides, and reaction conditions. The authors mainly reviewed the two kinds of radionuclide labeling strategies, chelator-based and chelator-free radiolabeling, as well as their advantages and disadvantages, in order to provide assistance for the labeling of different nanocarriers with radioactive nuclides for nuclide diagnosis and treatment.
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Key words:
- Radioisotopes /
- Nanoconjugates /
- Isotope labeling
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[1] 兰晓莉, 安锐. 分子影像靶向诊断与治疗——恶性肿瘤精准诊疗的利器[J]. 中华核医学与分子影像杂志, 2020, 40(5): 257−259. DOI: 10.3760/cma.j.cn321828-20200323-00121.
Lan XL, An R. Molecular imaging and targeted therapy: a powerful tool for accurate diagnosis and treatment of malignant tumors[J]. Chin J Nucl Med Mol Imaging, 2020, 40(5): 257−259. DOI: 10.3760/cma.j.cn321828-20200323-00121.[2] 孙一文, 赵晋华. PET分子影像探针纳米颗粒的研发与应用现状[J]. 中华核医学杂志, 2011, 31(5): 357−360. DOI: 10.3760/cma.j.issn.2022.05.022.
Sun YW, Zhao JH. Research and application status of PET molecular imaging probe nanoparticles[J]. Chin J Nucl Med, 2011, 31(5): 357−360. DOI: 10.3760/cma.j.issn.2022.05.022.[3] Pei P, Liu T, Shen WH, et al. Biomaterial-mediated internal radioisotope therapy[J]. Mater Horiz, 2021, 8(5): 1348−1366. DOI: 10.1039/d0mh01761b. [4] Smith BR, Gambhir SS. Nanomaterials for in vivo imaging[J]. Chem Rev, 2017, 117(3): 901−986. DOI: 10.1021/acs.chemrev.6b00073. [5] Ma WH, Fu FF, Zhu JY, et al. 64Cu-labeled multifunctional dendrimers for targeted tumor PET imaging[J]. Nanoscale, 2018, 10(13): 6113−6124. DOI: 10.1039/c7nr09269e. [6] Wei WJ, Rosenkrans ZT, Liu JJ, et al. ImmunoPET: concept, design, and applications[J]. Chem Rev, 2020, 120(8): 3787−3851. DOI: 10.1021/acs.chemrev.9b00738. [7] Holik HA, Ibrahim FM, Elaine AA, et al. The chemical scaffold of Theranostic radiopharmaceuticals: radionuclide, bifunctional chelator, and Pharmacokinetics modifying linker[J/OL]. Molecules, 2022, 27(10): 3062[2022-10-16]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143622/. DOI: 10.3390/mole-cules27103062. [8] Tang T, Wei YS, Yang QL, et al. Rapid chelator-free radiolabeling of quantum dots for in vivo imaging[J]. Nanoscale, 2019, 11(46): 22248−22254. DOI: 10.1039/c9nr08508d. [9] Chen CC, Chan YH, Lin SL, et al. Theranostic radiolabeled nanomaterials for molecular imaging and potential immunomodulation effects[J]. J Med Biol Eng, 2022, 42(5): 555−578. DOI: 10.1007/s40846-022-00715-6. [10] Pretze M, van der Meulen NP, Wangler C, et al. Targeted 64Cu-labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging[J]. J Label Compd Radiopharm, 2019, 62(8): 471−482. DOI: 10.1002/jlcr.3736. [11] Tian M, Lu W, Zhang R, et al. Tumor uptake of hollow gold nanospheres after intravenous and intra-arterial injection: PET/CT study in a rabbit VX2 liver cancer model[J]. Mol Imaging Biol, 2013, 15(5): 614−624. DOI: 10.1007/s11307-013-0635-x. [12] Zhang Y, Wang GL, Li Q, et al. Acidity-activated charge conversion of 177Lu-labeled Nanoagent for the enhanced photodynamic radionuclide therapy of cancer[J]. ACS Appl Mater Interfaces, 2022, 14(3): 3875−3884. DOI: 10.1021/acsami.1c21860. [13] Zhang XL, Chen F, Turker MZ, et al. Targeted melanoma radiotherapy using ultrasmall 177Lu-labeled α-melanocyte stimulating hormone-functionalized core-shell silica nanoparticles[J]. Biomaterials, 2020, 241: 119858. DOI: 10.1016/j.biomaterials.2020.119858. [14] Stéen EJL, Edem PE, Nørregaard K, et al. Pretargeting in nuclear imaging and radionuclide therapy: improving efficacy of theranostics and nanomedicines[J]. Biomaterials, 2018, 179: 209−245. DOI: 10.1016/j.biomaterials.2018.06.021. [15] Stéen EJL, Jørgensen JT, Johann K, et al. Trans-cyclooctene-functionalized peptobrushes with improved reaction kinetics of the tetrazine ligation for pretargeted nuclear imaging[J]. ACS Nano, 2020, 14(1): 568−584. DOI: 10.1021/acsnano.9b06905. [16] Man Au K, Tripathy A, Pe-I Lin C, et al. Bespoke pretargeted nanoradioimmunotherapy for the treatment of non-Hodgkin lymphoma[J]. ACS Nano, 2018, 12(2): 1544−1563. DOI: 10.1021/acsnano.7b08122. [17] Majkowska-Pilip A, Gawęda W, Żelechowska-Matysiak K, et al. Nanoparticles in targeted alpha therapy[J/OL]. Nanomaterials, 2020, 10(7): 1366[2022-10-16]. https://www.mdpi.com/2079-4991/10/7/1366. DOI: 10.3390/nano10071366. [18] Chen F, Ellison PA, Lewis CM, et al. Chelator-free synthesis of a dual-modality PET/MRI agent[J]. Angew Chem Int Ed, 2013, 52(50): 13319−13323. DOI: 10.1002/anie.201306306. [19] Ni DL, Jiang DW, Ehlerding EB, et al. Radiolabeling silica-based nanoparticles via coordination chemistry: basic principles, strategies, and applications[J]. Acc Chem Res, 2018, 51(3): 778−788. DOI: 10.1021/acs.accounts.7b00635. [20] Shaffer TM, Harmsen S, Khwaja E, et al. Stable radiolabeling of sulfur-functionalized silica nanoparticles with copper-64[J]. Nano Lett, 2016, 16(9): 5601−5604. DOI: 10.1021/acs.nanolett.6b02161. [21] Shi SX, Xu C, Yang K, et al. Chelator-free radiolabeling of nanographene: breaking the stereotype of chelation[J]. Angew Chem Int Ed, 2017, 56(11): 2889−2892. DOI: 10.1002/anie.201610649. [22] Chao Y, Wang GL, Liang C, et al. Rhenium-188 labeled tungsten disulfide nanoflakes for self-sensitized, near-infrared enhanced radioisotope therapy[J]. Small, 2016, 12(29): 3967−3975. DOI: 10.1002/smll.201601375. [23] Ognjanović M, Radović M, Mirković M, et al. 99mTc-, 90Y-, and 177Lu-labeled iron oxide nanoflowers designed for potential use in dual magnetic hyperthermia/radionuclide cancer therapy and diagnosis[J]. ACS Appl Mater Interfaces, 2019, 11(44): 41109−41117. DOI: 10.1021/acsami.9b16428. [24] Lamb J, Holland JP. Advanced methods for radiolabeling multimodality nanomedicines for SPECT/MRI and PET/MRI[J]. J Nucl Med, 2018, 59(3): 382−389. DOI: 10.2967/jnumed.116.187419. [25] Wang ZT, Huang P, Jacobson O, et al. Biomineralization-inspired synthesis of copper sulfide-ferritin Nanocages as cancer theranostics[J]. ACS Nano, 2016, 10(3): 3453−3460. DOI: 10.1021/acsnano.5b07521. [26] Sun XL, Cai WB, Chen XY. Positron emission tomography imaging using radiolabeled inorganic nanomaterials[J]. Acc Chem Res, 2015, 48(2): 286−294. DOI: 10.1021/ar500362y. [27] Zhao YF, Detering L, Sultan D, et al. Gold nanoclusters doped with 64Cu for CXCR4 positron emission tomography imaging of breast cancer and metastasis[J]. ACS Nano, 2016, 10(6): 5959−5970. DOI: 10.1021/acsnano.6b01326. [28] Heo GS, Zhao YF, Sultan D, et al. Assessment of copper nanoclusters for accurate in vivo tumor imaging and potential for translation[J]. ACS Appl Mater Interfaces, 2019, 11(22): 19669−19678. DOI: 10.1021/acsami.8b22752. [29] Zhang XH, Detering L, Sultan D, et al. CC chemokine receptor 2-targeting copper nanoparticles for positron emission tomography-guided delivery of gemcitabine for pancreatic ductal adenocarcinoma[J]. ACS Nano, 2021, 15(1): 1186−1198. DOI: 10.1021/acsnano.0c08185. [30] Wong RM, Gilbert DA, Liu K, et al. Rapid size-controlled synthesis of dextran-coated, 64Cu-doped iron oxide nanoparticles[J]. ACS Nano, 2012, 6(4): 3461−3467. DOI: 10.1021/nn300494k. [31] Sun XL, Huang XL, Guo JX, et al. Self-illuminating 64Cu-doped CdSe/ZnS Nanocrystals for in vivo tumor imaging[J]. J Am Chem Soc, 2014, 136(5): 1706−1709. DOI: 10.1021/ja410438n. [32] Pellico J, Ruiz-Cabello J, Saiz-Alía M, et al. Fast synthesis and bioconjugation of 68Ga core-doped extremely small iron oxide nanoparticles for PET/MR imaging[J]. Contrast Media Mol Imaging, 2016, 11(3): 203−210. DOI: 10.1002/cmmi.1681. [33] da Silva WM, de Andrade Alves E Silva RH, Cipreste MF, et al. Boron nitride nanotubes radiolabeled with 153Sm and 159Gd: potential application in nanomedicine[J]. Appl Radiat Isot, 2020, 157: 109032. DOI: 10.1016/j.apradiso.2019.109032. [34] Karpf MA. A phase III clinical trial of intra-arterial yttrium-90 glass microspheres in the treatment of patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2015, 33(S3): 477. DOI: 10.1200/jco.2015.33.3_suppl.477. [35] Jernigan SR, Osborne JA, Mirek CJ, et al. Selective internal radiation therapy: quantifying distal penetration and distribution of resin and glass microspheres in a surrogate arterial model[J]. J Vasc Interv Radiol, 2015, 26(6): 897−904.e2. DOI: 10.1016/j.jvir.2015.02.022. [36] Su WW, Chen C, Wang T, et al. Radionuclide-labeled gold nanoparticles for nuclei-targeting internal radio-immunity therapy[J]. Mater Horiz, 2020, 7(4): 1115−1125. DOI: 10.1039/c9mh01725a. [37] Yi X, Shen ML, Liu XP, et al. Diagnostic radionuclides labeled on biomimetic nanoparticles for enhanced follow-up photothermal therapy of cancer[J]. Adv Healthc Mater, 2021, 10(20): 2100860. DOI: 10.1002/adhm.202100860. [38] Karpov T, Postovalova A, Akhmetova D, et al. Universal chelator-free radiolabeling of organic and inorganic-based nanocarriers with diagnostic and therapeutic isotopes for internal radiotherapy[J]. Chem Mater, 2022, 34(14): 6593−6605. DOI: 10.1021/acs.chemmater.2c01507.
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