前沿述评

核酸适体药物偶联物——肿瘤精准治疗新风向

  • 韩永琪 ,
  • 韩达 ,
  • 閤谦 ,
  • 姬丁坤 ,
  • 谭蔚泓
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  • 1.上海交通大学医学院附属仁济医院分子医学研究院,上海 200127
    2.上海师范大学化学与材料科学学院,上海 200234
韩永琪(1999—),男,硕士生;电子信箱:hjydyx413228@163.com
閤 谦,电子信箱:kara_xia@hotmail.com
姬丁坤,电子信箱:dingkunji@sjtu.edu.cn
谭蔚泓,电子信箱:tan@hnu.edu.cn

收稿日期: 2022-05-18

  录用日期: 2022-08-18

  网络出版日期: 2022-09-28

基金资助

上海市自然科学基金面上项目(22ZR1437800);上海市青年科技英才扬帆计划(20YF1424500)

Aptamer-drug conjugates (ApDCs): new trend for cancer precision therapy

  • Yongqi HAN ,
  • Da HAN ,
  • Qian XIA ,
  • Dingkun JI ,
  • Weihong TAN
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  • 1.Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    2.College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China
XIA Qian, E-mail:kara_xia@hotmail.com.
JI Dingkun, E-mail: dingkunji@sjtu.edu.cn
TAN Weihong, E-mail: tan@hnu.edu.cn

Received date: 2022-05-18

  Accepted date: 2022-08-18

  Online published: 2022-09-28

Supported by

Natural Science Foundation of Shanghai(22ZR1437800);Shanghai Sailing Program(20YF1424500)

摘要

癌症严重威胁人类的生命健康,癌症的精准治疗至今仍是亟须解决的重大医学难题。精准分子医学,可从分子水平上诊断和治疗肿瘤,为肿瘤诊疗提供新的策略。作为优异的靶向识别分子和药物递送载体,核酸适体及核酸适体偶联物为肿瘤的精准治疗提供了重要的分子工具,已成为肿瘤靶向治疗的前沿新兴领域。该文综述了核酸适体性质及筛选技术、核酸适体药物偶联物的构建及其在临床肿瘤靶向治疗中的应用,并对核酸适体药物在肿瘤精准分子医学中的发展前景进行展望,以期为新型分子靶向药物的开发及其在临床恶性肿瘤治疗中的应用提供新的思路。

本文引用格式

韩永琪 , 韩达 , 閤谦 , 姬丁坤 , 谭蔚泓 . 核酸适体药物偶联物——肿瘤精准治疗新风向[J]. 上海交通大学学报(医学版), 2022 , 42(9) : 1176 -1181 . DOI: 10.3969/j.issn.1674-8115.2022.09.003

Abstract

Cancer is a worldwide medical issue that seriously threatens human health. Precision molecular medicine provides a new strategy for cancer theranostics. As excellent targeting recognition molecules and drug delivery platforms, aptamers and aptamer drug-conjugates (ApDCs) have provided a series of useful molecular tools for cancer precision therapy. In this paper, the properties and the selection techniques of aptamers, the construction of ApDCs and their applications to clinical tumor-targeting therapy are reviewed. Additionally, the challenges and perspective of ApDCs in precision molecular medicine for cancers are presented. This review may provide new horizons for molecular-targeted anti-tumor drugs in the therapy of clinical malignant tumors.

参考文献

1 SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33.
2 SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33.
3 FERLAY J, COLOMBET M, SOERJOMATARAM I, et al. Cancer statistics for the year 2020: an overview[J]. Int J Cancer, 2021, 149(4): 778-789.
4 潘锋, 张清涵. 科技创新助力肿瘤精准医学发展[J]. 中国医药科学, 2021, 11(24): 1-5.
4 PAN F, ZHANG Q H. Technological innovation facilitates the development of precision tumor medicine[J]. Chin Med Pharm, 2021, 11(24): 1-5.
5 谭蔚泓, 徐海燕, 刘艳岚, 等. 分子医学助力健康中国[J]. 肿瘤学杂志, 2021, 27(1): 1-3.
5 TAN W H, XU H Y, LIU Y L, et al. Molecular medicine contributes to healthy China[J]. J Chin Oncol, 2021, 27(1): 1-3.
6 KIM D H, SEO J M, SHIN K J, et al. Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy[J]. Biomater Res, 2021, 25(1): 42.
7 XUAN W, PENG Y, DENG Z, et al. A basic insight into aptamer-drug conjugates (ApDCs)[J]. Biomaterials, 2018, 182: 216-226.
8 ELLINGTON A D, SZOSTAK J W. In vitro selection of RNA molecules that bind specific ligands[J]. Nature, 1990, 346(6287): 818-822.
9 TUERK C, GOLD L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase[J]. Science, 1990, 249(4968): 505-510.
10 ZHU G, NIU G, CHEN X. Aptamer-drug conjugates[J]. Bioconjug Chem, 2015, 26(11): 2186-2197.
11 SEFAH K, SHANGGUAN D, XIONG X, et al. Development of DNA aptamers using cell-SELEX[J]. Nat Protoc, 2010, 5(6): 1169-1185.
12 NI S, ZHUO Z, PAN Y, et al. Recent progress in aptamer discoveries and modifications for therapeutic applications[J]. ACS Appl Mater Interfaces, 2021, 13(8): 9500-9519.
13 ZHU G, CHEN X. Aptamer-based targeted therapy[J]. Adv Drug Deliv Rev, 2018, 134: 65-78.
14 SOUNDARARAJAN S, CHEN W, SPICER EK, et al. The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells[J]. Cancer Res, 2008, 68(7): 2358-2365.
15 ZHU C, YANG G, GHULAM M, et al. Evolution of multi-functional capillary electrophoresis for high-efficiency selection of aptamers[J]. Biotechnol Adv, 2019, 37(8): 107432.
16 WU Y X, KWON Y J. Aptamers: the “evolution” of SELEX[J]. Methods, 2016, 106: 21-28.
17 BEREZOVSKI M V, MUSHEEV M U, DRABOVICH A P, et al. Non-SELEX: selection of aptamers without intermediate amplification of candidate oligonucleotides[J]. Nat Protoc, 2006, 1(3): 1359-1369.
18 JEONG S, HAN S R, LEE Y J, et al. Selection of RNA aptamers specific to active prostate-specific antigen[J]. Biotechnol Lett, 2010, 32(3): 379-385.
19 YANG X, LI N, GORENSTEIN D G. Strategies for the discovery of therapeutic aptamers[J]. Expert Opin Drug Discov, 2011, 6(1): 75-87.
20 BAGALKOT V, FAROKHZAD O C, LANGER R, et al. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform[J]. Angew Chem Int Ed Engl, 2006, 45(48): 8149-8152.
21 HU Y, DUAN J, ZHAN Q, et al. Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro[J]. PLoS One, 2012, 7(2): e31970.
22 LIU Z, DUAN J H, SONG Y M, et al. Novel HER2 aptamer selectively delivers cytotoxic drug to HER2-positive breast cancer cells in vitro[J]. J Transl Med, 2012, 10: 148.
23 HUANG Y F, SHANGGUAN D, LIU H, et al. Molecular assembly of an aptamer-drug conjugate for targeted drug delivery to tumor cells[J]. Chembiochem, 2009, 10(5): 862-868.
24 ZHOU F, WANG P, PENG Y, et al. Molecular engineering-based aptamer-drug conjugates with accurate tunability of drug ratios for drug combination targeted cancer therapy[J]. Angew Chem Int Ed Engl, 2019, 58(34): 11661-11665.
25 HE J, PENG T, PENG Y, et al. Molecularly engineering triptolide with aptamers for high specificity and cytotoxicity for triple-negative breast cancer[J]. J Am Chem Soc, 2020, 142(6): 2699-2703.
26 YANG Q, DENG Z, WANG D, et al. Conjugating aptamer and mitomycin C with reductant-responsive linker leading to synergistically enhanced anticancer effect[J]. J Am Chem Soc, 2020, 142(5): 2532-2540.
27 WANG R, ZHU G, MEI L, et al. Automated modular synthesis of aptamer-drug conjugates for targeted drug delivery[J]. J Am Chem Soc, 2014, 136(7): 2731-2734.
28 JIN C, ZHANG H, ZOU J, et al. Floxuridine homomeric oligonucleotides “hitchhike” with albumin in?situ for cancer chemotherapy[J]. Angew Chem Int Ed Engl, 2018, 57(29): 8994-8997.
29 XUAN W, XIA Y, LI T, et al. Molecular self-assembly of bioorthogonal aptamer-prodrug conjugate micelles for hydrogen peroxide and pH-independent cancer chemodynamic therapy[J]. J Am Chem Soc, 2020, 142(2): 937-944.
30 YANG Y, HE J, ZHU W, et al. Molecular domino reactor built by automated modular synthesis for cancer treatment[J]. Theranostics, 2020, 10(9): 4030-4041.
31 GAO F, ZHOU J, SUN Y, et al. Programmable repurposing of existing drugs as pharmaceutical elements for the construction of aptamer-drug conjugates[J]. ACS Appl Mater Interfaces, 2021, 13(8): 9457-9463.
32 YANG C, ZHAO H, SUN Y, et al. Programmable manipulation of oligonucleotide-albumin interaction for elongated circulation time[J]. Nucleic Acids Res, 2022, 50(6): 3083-3095.
33 NI X, CASTANARES M, MUKHERJEE A, et al. Nucleic acid aptamers: clinical applications and promising new horizons[J]. Curr Med Chem, 2011, 18(27): 4206-4214.
34 NG E W, SHIMA D T, CALIAS P, et al. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease[J]. Nat Rev Drug Discov, 2006, 5(2): 123-132.
35 周灵丽, 叶茂. 核酸适配体介导的肿瘤免疫治疗研究进展[J]. 生物化学与生物物理进展, 2022, 49(6): 1036-1044.
35 ZHOU L L, YE M. Research progress of aptamer-mediated tumor immunotherapy[J]. Prog Biochem Biophys, 2022, 49(6): 1036-1044.
36 HARBECK N, PENAULT-LLORCA F, CORTES J, et al. Breast cancer[J]. Nat Rev Dis Prim, 2019, 5(1): 66.
37 YOON S, ARMSTRONG B, HABIB N, et al. Blind SELEX approach identifies RNA aptamers that regulate EMT and inhibit metastasis[J]. Mol Cancer Res, 2017, 15(7): 811-820.
38 PARK J Y, CHO Y L, CHAE J R, et al. Gemcitabine-incorporated G-quadruplex aptamer for targeted drug delivery into pancreas cancer[J]. Mol Ther Nucleic Acids, 2018, 12: 543-553.
39 APTEKAR S, ARORA M, LAWRENCE C L, et al. Selective targeting to glioma with nucleic acid aptamers[J]. PLoS One, 2015, 10(8): e0134957.
40 WU Q, WANG Y, WANG H, et al. DNA aptamers from whole-cell SELEX as new diagnostic agents against glioblastoma multiforme cells[J]. Analyst, 2018, 143(10): 2267-2275.
41 LUO Z, YAN Z, JIN K, et al. Precise glioblastoma targeting by AS1411 aptamer-functionalized poly (L?γ?glutamylglutamine)?paclitaxel nanoconjugates[J]. J Colloid Interface Sci, 2017, 490: 783-796.
42 ZHAO N, PEI S N, QI J, et al. Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia[J]. Biomaterials, 2015, 67: 42-51.
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