中文
Earlier issues
Announcement
More
Progress in Chemistry 2022, Vol. 34 Issue (4): 837-845 DOI: 10.7536/PC210446 Previous Articles   Next Articles

• Review •

Self-Assembly of Small Molecule Modified DNA and Their Application in Biomedicine

Jiahui Ma1, Wei Yuan1, Simin Liu1, Zhiyong Zhao1,2()   

  1. 1 The State Key Laboratory of Refractories and Metallurgy, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology,Wuhan 430081, China
    2 Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Hubei Normal University,Huangshi 435002, China
  • Received: Revised: Online: Published:
  • Contact: Zhiyong Zhao
  • Supported by:
    National Natural Science Foundation of China(21604066); National Natural Science Foundation of China(21871216); Research Project of Hubei Provincial Department of Education(B2016012)
Richhtml ( 20 ) PDF ( 233 ) Cited
Export

EndNote

Ris

BibTeX

Due to the addressability, programmability and excellent biocompatibility, DNA has been applied not merely in constructing static elegant nanostructures with different shapes and sizes, but also in designing dynamic nanodevices. Moreover, to further expand the application of DNA, functional groups or molecules can be conjugated with DNA through chemical modification. DNA could combine with hydrophobic organic molecules to be a new amphiphilic building block and then self-assemble into nanomaterials. So far, DNA has been covalent with polymers, dendrimers, peptides or proteins, and the assembly behavior and potential application of these hybrids have been widely investigated. Of particular note, recent state-of-the-art research has turned our attention to the amphiphilic DNA organic hybrids, including small molecule modified DNA (lipid-DNA, fluorescent molecule-DNA, etc.). This review focuses mainly on the development of their self-assembly behavior and their potential application in biomedicine. The potential challenges regarding the amphiphilic DNA organic hybrids are also briefly discussed, aiming to advance their practical applications in nanoscience and biomedicine.

Contents

1 Introduction

2 Self-assembly of small molecule modified DNA

2.1 Self-assembly of amphiphilic DNA-small molecule hybrid

2.2 Self-assembly of supramolecular DNA amphiphiles through host-guest interaction

3 Application of small molecule modified DNA assemblies in biomedicine

3.1 Drug release

3.2 Target delivery

3.3 Biosensor

4 Conclusion and outlook

Key words: small molecule modified DNA, conjugate, assembly and control, biomedicine application
Fig. 1 (a) DNA-programmed lipid assembles to form spherical lamellar vesicles capable of switching phase to form small spherical micelles in a fully reversible fashion via DNA hybridization (+ DNA2 ) and strand invasion (+ DNA3 ) cycles[32]. (b)Schematic of stability-tunable DNA micelles. Intermolecular G-quadruplex stabilizes DNA micelles against disruption by serum albumin. Upon exposure to UV light, C6-cDNA is released to block the formation of G-quadruplex, resulting in the dissociation of micelles in serum albumin[34]
Fig. 2 (a) The self-assembly process of D18-PDI conjugates and the reversible morphological change based on the host-guest interaction[38]. Reproduced from Ref. [38] with permission from The Royal Society of Chemistry. (b) A DNA-grafted supramolecular polymer and the chemical structure of pyrene units[40]
Fig. 3 (a) Solid-phase “click” chemistry approach for the synthesis of DNA1~3 amphiphiles and their reversible self-assembly into surface-engineered vesicles with enhanced emission[43]. (b) Schematic for the self-assembly of DNA-based amphiphiles into DNA-decorated, twisted nanoribbons with M-helicity[47]
Fig. 4 (a) Schematic representation illustrating the “click” chemistry based synthesis of DNA1 or -2-β-CD and non-covalent synthesis of DNA1 or -2-β-CD/1 or 2. Amphiphilicity-driven self-assembly of DNA1 or -2-β-CD/1 or 2 into DNA-decorated vesicles is also shown[52]. Reproduced from Ref. [52] with permission from The Royal Society of Chemistry.(b)The modular construction and self-assembly of DNA supra-amphiphiles through host-guest interaction and their stimuli responsiveness[54]
Fig. 5 (a) Working principle of switchable aptamer micelle flares. In the absence of target, the aptamer switch probe maintains a loop-stemstructure, and fluorescence is quenched. Upontarget binding, the conformation of switchable aptamer is altered, resulting in the restoration of fluorescence signal[57]. (b) Schematics of the DNA-drug nanostructures assembled from photolabile DNA-drug amphiphiles[59]. (c) Chemical structure of DNA-PE and a schematic representation depicting the amphiphilicity-driven self-assembly of DNA-PE into vesicular nanostructures, and their cellular uptake[61]
[1]
Seeman N C. J. Theor. Biol., 1982, 99(2): 237.

pmid: 6188926
[2]
Seeman N C. Nature, 2003, 421(6921): 427.

doi: 10.1038/nature01406
[3]
Rothemund P W K. Nature, 2006, 440(7082): 297.

doi: 10.1038/nature04586
[4]
Douglas S M, Dietz H, Liedl T, Högberg B, Graf F, Shih W M. Nature, 2009, 459(7245): 414.

doi: 10.1038/nature08016
[5]
Han D R, Pal S, Nangreave J, Deng Z T, Liu Y, Yan H. Science, 2011, 332(6027): 342.

doi: 10.1126/science.1202998
[6]
Fu J L, Liu M H, Liu Y, Yan H. Acc. Chem. Res., 2012, 45(8): 1215.

doi: 10.1021/ar200295q
[7]
Wang P F, Meyer T A, Pan V, Dutta P K, Ke Y G. Chem, 2017, 2(3): 359.

doi: 10.1016/j.chempr.2017.02.009
[8]
Nummelin S, Kommeri J, Kostiainen M A, Linko V. Adv. Mater., 2018, 30(24): 1703721.

doi: 10.1002/adma.201703721
[9]
Yurke B, Turberfield A J, Mills A P, Simmel F C, Neumann J L. Nature, 2000, 406(6796): 605.

doi: 10.1038/35020524
[10]
Yan H, Zhang X P, Shen Z Y, Seeman N C. Nature, 2002, 415(6867): 62.

doi: 10.1038/415062a
[11]
Liu H J, Liu D S. Chem. Commun., 2009(19): 2625.
[12]
Krishnan Y, Simmel F C. Angew. Chem. Int. Ed., 2011, 50(14): 3124.

doi: 10.1002/anie.200907223 pmid: 21432950
[13]
Shao Y, Jia H Y, Cao T Y, Liu D S. Acc. Chem. Res., 2017, 50(4): 659.

doi: 10.1021/acs.accounts.6b00524
[14]
Gačanin J, Synatschke C V, Weil T. Adv. Funct. Mater., 2020, 30(4): 1906253.

doi: 10.1002/adfm.201906253
[15]
Jiang Q, Liu S L, Liu J B, Wang Z G, Ding B Q. Adv. Mater., 2019, 31(45): 1804785.

doi: 10.1002/adma.201804785
[16]
Hu Q Q, Li H, Wang L H, Gu H Z, Fan C H. Chem. Rev., 2019, 119(10): 6459.

doi: 10.1021/acs.chemrev.7b00663
[17]
Shen H J, Wang Y Q, Wang J, Li Z H, Yuan Q. ACS Appl. Mater. Interfaces, 2019, 11(15): 13859.

doi: 10.1021/acsami.8b06175
[18]
Rizzuto F J, Trinh T, Sleiman H F. Chem, 2020, 6(7): 1560.

doi: 10.1016/j.chempr.2020.06.012
[19]
Schnitzler T, Herrmann A. Acc. Chem. Res., 2012, 45(9): 1419.

doi: 10.1021/ar200211a
[20]
Pan G F, Jin X, Mou Q B, Zhang C. Chin. Chem. Lett., 2017, 28(9): 1822.

doi: 10.1016/j.cclet.2017.08.022
[21]
Zhao Z Y, Du T, Liang F, Liu S M. Int. J. Mol. Sci., 2018, 19(8): 2283.

doi: 10.3390/ijms19082283
[22]
Saccà B, Niemeyer C M. Chem. Soc. Rev., 2011, 40(12): 5910.

doi: 10.1039/c1cs15212b
[23]
Stephanopoulos N. Bioconjugate Chem., 2019, 30(7): 1915.

doi: 10.1021/acs.bioconjchem.9b00259 pmid: 31082220
[24]
Dong Y C, Liu D S, Yang Z Q. Methods, 2014, 67(2): 116.

doi: 10.1016/j.ymeth.2013.11.004
[25]
El-Sagheer A H, Brown T. Chem. Soc. Rev., 2010, 39(4): 1388.

doi: 10.1039/b901971p pmid: 20309492
[26]
Safak M, Alemdaroglu F E, Li Y, Ergen E, Herrmann A. Adv. Mater., 2007, 19(11): 1499.

doi: 10.1002/adma.200700240
[27]
Averick S E, Dey S K, Grahacharya D, Matyjaszewski K, Das S R. Angew. Chem. Int. Ed., 2014, 53(10): 2739.

doi: 10.1002/anie.201308686
[28]
Liu K, Zheng L F, Liu Q, de Vries J W, Gerasimov J Y, Herrmann A. J. Am. Chem. Soc., 2014, 136(40): 14255.

doi: 10.1021/ja5080486
[29]
Trinh T, Chidchob P, Bazzi H S, Sleiman H F. Chem. Commun., 2016, 52(72): 10914.

doi: 10.1039/C6CC04970B
[30]
Gosse C, Boutorine A, Aujard I, Chami M, Kononov A, CognÉ-Laage E, Allemand J F, Li J, Jullien L. J. Phys. Chem. B, 2004, 108(20): 6485.

doi: 10.1021/jp031188m
[31]
Dentinger P M, Simmons B A, Cruz E, Sprague M. Langmuir, 2006, 22(7): 2935.

pmid: 16548535
[32]
Thompson M P, Chien M P, Ku T H, Rush A M, Gianneschi N C. Nano Lett., 2010, 10(7): 2690.

doi: 10.1021/nl101640k pmid: 20518544
[33]
Yan Y F, Sun Y W, Yu H Y, Xu H, Lu J R. Soft Matter, 2015, 11(9): 1748.

doi: 10.1039/C4SM02499K
[34]
Jin C, Liu X J, Bai H R, Wang R W, Tan J, Peng X H, Tan W H. ACS Nano, 2017, 11(12): 12087.

doi: 10.1021/acsnano.7b04882
[35]
Abdalla M A, Bayer J, Rädler J O, Müllen K. Angew. Chem. Int. Ed., 2004, 43(30): 3967.

doi: 10.1002/anie.200353621
[36]
Neelakandan P P, Pan Z Z, Hariharan M, Zheng Y, Weissman H, Rybtchinski B, Lewis F D. J. Am. Chem. Soc., 2010, 132(44): 15808.

doi: 10.1021/ja1076525 pmid: 20954733
[37]
Mishra A K, Weissman H, Krieg E, Votaw K A, McCullagh M, Rybtchinski B, Lewis F D. Chem. Eur. J., 2017, 23(43): 10328.

doi: 10.1002/chem.201700752
[38]
Du T, Yuan W, Zhao Z Y, Liu S M. Chem. Commun., 2019, 55(25): 3658.

doi: 10.1039/C9CC00406H
[39]
Bittermann H, Siegemund D, Malinovskii V L, Häner R. J. Am. Chem. Soc., 2008, 130(46): 15285.

doi: 10.1021/ja806747h pmid: 18950164
[40]
Vyborna Y, Vybornyi M, Rudnev A V, Häner R. Angew. Chem. Int. Ed., 2015, 54(27): 7934.

doi: 10.1002/anie.201502066 pmid: 25960306
[41]
Vyborna Y, Vybornyi M, Häner R. J. Am. Chem. Soc., 2015, 137(44): 14051.

doi: 10.1021/jacs.5b09889 pmid: 26491956
[42]
Vyborna Y, Vybornyi M, Häner R. Chem. Commun., 2017, 53(37): 5179.

doi: 10.1039/C7CC00886D
[43]
Albert S K, Thelu H V P, Golla M, Krishnan N, Chaudhary S, Varghese R. Angew. Chem. Int. Ed., 2014, 53(32): 8352.

doi: 10.1002/anie.201403455 pmid: 24962762
[44]
Albert S K, Golla M, Thelu H V P, Krishnan N, Varghese R. Chem. Eur. J., 2017, 23(35): 8348.

doi: 10.1002/chem.201701446
[45]
Gu R P, Lamas J, Rastogi S K, Li X P, Brittain W, Zauscher S. Colloids Surf. B: Biointerfaces, 2015, 135: 126.

doi: 10.1016/j.colsurfb.2015.07.010
[46]
Albert S K, Sivakumar I, Golla M, Thelu H V P, Krishnan N, Joseph Libin K L, Ashish, Varghese R. J. Am. Chem. Soc., 2017, 139(49): 17799.

doi: 10.1021/jacs.7b09283 pmid: 29232955
[47]
Golla M, Albert S K, Atchimnaidu S, Perumal D, Krishnan N, Varghese R. Angew. Chem. Int. Ed., 2019, 58(12): 3865.

doi: 10.1002/anie.201813900
[48]
Bösch C D, Jevric J, Bürki N, Probst M, Langenegger S M, Häner R. Bioconjugate Chem., 2018, 29(5): 1505.

doi: 10.1021/acs.bioconjchem.8b00263
[49]
Zhang X, Wang C. Chem. Soc. Rev., 2011, 40(1): 94.

doi: 10.1039/b919678c pmid: 20890490
[50]
Zhu H, Shangguan L Q, Shi B B, Yu G C, Huang F H. Mater. Chem. Front., 2018, 2(12): 2152.

doi: 10.1039/C8QM00314A
[51]
Chiba J Y, Sakai A, Yamada S, Fujimoto K, Inouye M. Chem. Commun., 2013, 49(57): 6454.

doi: 10.1039/c3cc43109f
[52]
Albert S K, Thelu H V P, Golla M, Krishnan N, Varghese R. Nanoscale, 2017, 9(17): 5425.

doi: 10.1039/c6nr08370f pmid: 28300237
[53]
Thelu H V P, Albert S K, Golla M, Krishnan N, Ram D, Srinivasula S M, Varghese R. Nanoscale, 2018, 10(1): 222.

doi: 10.1039/C7NR06985E
[54]
Yuan W, Ma J H, Zhao Z Y, Liu S M. Macromol. Rapid Commun., 2020, 41(9): 2000022.

doi: 10.1002/marc.202000022
[55]
Wu S X, Li J, Liang H, Wang L P, Chen X, Jin G X, Xu X P, Yang H H. Sci. China Chem., 2017, 60(5): 628.

doi: 10.1007/s11426-016-0351-5
[56]
Liu H P, Zhu Z, Kang H Z, Wu Y R, Sefan K, Tan W H. Chem. Eur. J., 2010, 16(12): 3791.

doi: 10.1002/chem.200901546
[57]
Wu C C, Chen T, Han D, You M X, Peng L, Cansiz S, Zhu G Z, Li C M, Xiong X L, Jimenez E, Yang C J, Tan W H. ACS Nano, 2013, 7(7): 5724.

doi: 10.1021/nn402517v
[58]
Pokholenko O, Gissot A, Vialet B, Bathany K, ThiÉry A, BarthÉlÉmy P. J. Mater. Chem. B, 2013, 1(39): 5329.

doi: 10.1039/c3tb20357c pmid: 32263335
[59]
Tan X Y, Li B B, Lu X G, Jia F, Santori C, Menon P, Li H, Zhang B H, Zhao J J, Zhang K. J. Am. Chem. Soc., 2015, 137(19): 6112.

doi: 10.1021/jacs.5b00795
[60]
Chan M S, Tam D Y, Dai Z W, Liu L S, Ho J W T, Chan M L, Xu D, Wong M S, Tin C, Lo P K. Small, 2016, 12(6): 770.

doi: 10.1002/smll.201503051
[61]
Thelu H V P, Albert S K, Golla M, Krishnan N, Yamijala S B, Nair S V, Srinivasula S M, Varghese R. ChemistrySelect, 2016, 1(17): 5389.

doi: 10.1002/slct.201600897
[62]
Zhang Y, Zhang Y, Song G B, He Y L, Zhang X B, Liu Y, Ju H X. Angew. Chem. Int. Ed., 2019, 58(50): 18207.

doi: 10.1002/anie.201909870 pmid: 31583799
[63]
Choi K M, Kwon I C, Ahn H J. Biomaterials, 2013, 34(16): 4183.

doi: 10.1016/j.biomaterials.2013.02.044
[64]
Zou J M, Jin C, Wang R W, Kuai H L, Zhang L L, Zhang X B, Li J, Qiu L P, Tan W H. Anal. Chem., 2018, 90(11): 6843.

doi: 10.1021/acs.analchem.8b01005
[65]
Zhang P, Jiang J, Yuan R, Zhuo Y, Chai Y Q. J. Am. Chem. Soc., 2018, 140(30): 9361.

doi: 10.1021/jacs.8b04648 pmid: 30008212
[66]
Chen Z, Lu J X, Xiao F, Huang Y S, Zhang X J, Tian L L. Chem. Commun., 2020, 56(10): 1501.

doi: 10.1039/C9CC08093G
[67]
Hu Q Q, Li H, Wang L H, Gu H Z, Fan C H. Chem. Rev., 2019, 119(10): 6459.

doi: 10.1021/acs.chemrev.7b00663
[68]
Lacroix A, Sleiman H F. ACS Nano, 2021, 15(3): 3631.

doi: 10.1021/acsnano.0c06136
[1] Lin Chen, Jie-Feng Chen, Yi-Ren Liu, Yuyu Liu, Hai-Feng Ling, Ling-Hai Xie. Organic Strained Semiconductors and Their Optoelectronic Properties [J]. Progress in Chemistry, 2022, 34(8): 1772-1783.
[2] Yubing Wang, Jie Chen, Wei Yan, Jianwen Cui. Preparation and Application of Conjugated Microporous Polymers [J]. Progress in Chemistry, 2021, 33(5): 838-854.
[3] Ziru Sun, Shengnan Liu, Qingzhi Gao. Development of Anticancer Drugs Targeting Glucose Transporters(GLUTs) [J]. Progress in Chemistry, 2020, 32(12): 1869-1878.
[4] Ni Huang, Feng Xu, Jiangbin Xia. Solid State Polymerization of Polythiophene and Its Applications [J]. Progress in Chemistry, 2019, 31(8): 1103-1115.
[5] Qi-Feng Zhou, Bo Jiang*, Hai-Bo Yang*. Design and Synthesis of Conjugated Aromatic Macrocyclic Rings That Can Serve as Carbon Nanotube Segments [J]. Progress in Chemistry, 2018, 30(5): 628-638.
[6] Dandan Shi, Xisha Zhang, Deqing Zhang. Application of Organic Conjugated Frameworks Containing Seven-Membered Carbon Rings in Optoelectronic Materials [J]. Progress in Chemistry, 2018, 30(5): 658-672.
[7] Jin Du, Rui Liao, Xinglin Zhang, Huibin Sun, Wei Huang. The Classification of Electrofluorochromism Materials and Color Change Mechanisms [J]. Progress in Chemistry, 2018, 30(2/3): 286-294.
[8] Yijun Lin, Yunlong Zhu, Guichao Kuang, Guipeng Yu*, Riguang Jin. Application of Porous Organic Polymers in the Radioactive Iodine Adsorption [J]. Progress in Chemistry, 2017, 29(7): 766-775.
[9] Lu Xiaomei, Li Jie, Hu Wenbo, Deng Weixing, Fan Quli, Huang Wei. Recent Advances of the Water-Soluble Conjugated Polymer Brushes [J]. Progress in Chemistry, 2016, 28(4): 528-540.
[10] Sun Pengfei, Hou Huanzhi, Fan Quli, Huang Wei. Synthesis and Application of Water-Soluble Conjugated Glycopolymer [J]. Progress in Chemistry, 2016, 28(10): 1489-1500.
[11] Shu Xin, Li Zhaoxiang, Xia Jiangbin. Synthetic Methods for Poly(thiophene)s [J]. Progress in Chemistry, 2015, 27(4): 385-394.
[12] Tian Danbi, Zhang Wei, Tang Yan, Jiang Ling, Liu Jia, Hu Yi. Bioconjugate Probe for Enzyme Activity Based on the Gold Nanoparticles [J]. Progress in Chemistry, 2015, 27(2/3): 267-274.
[13] Xiong Lina, Zhang Xueqin, Sun Ying, Yang Hong. Synthesis, Self-Assembly and Application of All-Conjugated Block Copolymers [J]. Progress in Chemistry, 2015, 27(12): 1774-1783.
[14] Ma Yun, Zhou Yan, Du Wenqi, Miao Zhihui, Qi Zhengjian*. The Application of DNA Biosensor Based on Conjugated Polymers [J]. Progress in Chemistry, 2015, 27(12): 1799-1807.
[15] Chen Yun, Shao Ya, Fan Lijuan. Fluorescent Color Tuning of Conjugated Polymer Materials: Mechanisms and Methods [J]. Progress in Chemistry, 2014, 26(11): 1801-1810.