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Oligonucleotide–Polymer Conjugates: From Molecular Basics to Practical Application

Topics in Current Chemistry volume 378, Article number: 24 (2020) Cite this article

Abstract

DNA exhibits many attractive properties, such as programmability, precise self-assembly, sequence-coded biomedical functions, and good biocompatibility; therefore, DNA has been used extensively as a building block to construct novel nanomaterials. Recently, studies on oligonucleotide–polymer conjugates (OPCs) have attracted increasing attention. As hybrid molecules, OPCs exhibit novel properties, e.g., sophisticated self-assembly behaviors, which are distinct from the simple combination of the functions of DNA and polymer, making OPCs interesting and useful. The synthesis and applications of OPCs are highly dependent on the choice of the polymer block, but a systematic summary of OPCs based on their molecular structures is still lacking. In order to design OPCs for further applications, it is necessary to thoroughly understand the structure–function relationship of OPCs. In this review, we carefully categorize recently developed OPCs by the structures of the polymer blocks, and discuss the synthesis, purification, and applications for each category. Finally, we will comment on future prospects for OPCs.

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Insets b, c are adapted with permission from [103]

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Abbreviations

DNA:

Deoxyribonucleic acid

ODN:

Oligonucleotide

OPC:

Oligonucleotide–polymer conjugate

DX:

Double-crossover

siRNA:

Small interference RNA

RISC:

RNA-induced silencing complex

PLA:

Polylactic acid

PGA:

Polyglycolic acid

PLGA:

Poly (lactic-co-glycolic acid)

PCL:

Polycaprolactone

PASP:

Polyaspartic acid

PNIPAM:

Poly[N-isopropylacrylamide]

PEG:

Polyethylene glycol

DMSO:

Dimethyl sulfoxide

DMF:

Dimethylformamide

PS:

Polystyrene

CPG:

Controlled pore glass

PPE:

Poly-(phenylene–ethynylene)

HE:

Dodecanediol phosphoramidite

ATRP:

Atom transfer radical polymerization

RAFT:

Reversible addition-fragmentation chain transfer polymerization

CPADB:

4-Cyano-4-(phenylcarbonothioylthio) pentanoic acid

BTPA:

2-(Butylthiocarbonothioyl) propionic acid

EY:

Eosin Y

AscA:

Ascorbic acid

APS:

Ammonium persulfate

TEMED:

Tetramethylethylenediamine

PAGE:

Polyacrylamide gel electrophoresis

FDA:

Food and Drug Administration

PEI:

Polyethyleneimine

SNA:

Spherical nucleic acid

shRNA:

Short hairpin RNAs

RCT:

Rolling circle transcription

MDR1:

Multidrug resistance protein 1

DOX:

Doxorubicin

PPT-g-PEG:

Peptide-grafted poly (ethylene glycol)

Fc:

Ferrocene

MNP:

Magnetic nanoparticle

PNB:

Polynorbornene

PPO:

Polypropylene oxide

LCST:

Low critical solution temperature

VPTT:

Volume phase transition temperature

DMT:

Dimethoxytrityl

HPLC:

High performance liquid chromatography

PPE:

Poly (phenyleneethynylene)

HEX:

Hexachlorofluorescein

FRET:

Fluorescence Resonance Energy Transfer

SWNT:

Single-walled carbon nanotube

PFO:

Polyfluorene

PT:

Polythiophene

PFP:

Poly [fluorine-co-phenylene fluorene]

ACQ:

Aggregation caused quenching

APPV:

(2,5-Dialkoxy) paraphenylene vinylene

PAM:

Polyacrylamide

ROMP:

Ring-opening metathesis polymerization

pRNA:

Passenger-stranded RNA

References

  1. Fang WN, Jia SS, Chao J, Wang LQ, Duan XY, Liu HJ, Li Q, Zuo XL, Wang LH, Wang LH, Liu N, Fan CH (2019) Quantizing single-molecule surface-enhanced Raman scattering with DNA origami metamolecules. Sci Adv 5:eaau4506

    PubMed  PubMed Central  Google Scholar 

  2. Chen P, Zhang T, Zhou T, Liu D (2016) Number-controlled spatial arrangement of gold nanoparticles with DNA dendrimers. RSC Adv 6:70553–70556

    CAS  Google Scholar 

  3. Ponnuswamy N, Bastings MMC, Nathwani B, Ryu JH, Chou LYT, Vinther M, Li WA, Anastassacos FM, Mooney DJ, Shih WM (2017) Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation. Nat Commun 8:15654

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhang H, Wang Y, Zhang H, Liu X, Lee A, Huang Q, Wang F, Chao J, Liu H, Li J, Shi J, Zuo X, Wang L, Wang L, Cao X, Bustamante C, Tian Z, Fan C (2019) Programming chain-growth copolymerization of DNA hairpin tiles for in vitro hierarchical supramolecular organization. Nat Commun 10:1006

    PubMed  PubMed Central  Google Scholar 

  5. Seeman NC, Sleiman HF (2017) DNA nanotechnology. Nat Rev Mater 3:17068

    Google Scholar 

  6. Chidchob P, Sleiman HF (2018) Recent advances in DNA nanotechnology. Curr Opin Chem Biol 46:63–70

    CAS  PubMed  Google Scholar 

  7. Ohto U, Shibata T, Tanji H, Ishida H, Krayukhina E, Uchiyama S, Miyake K, Shimizu T (2015) Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9. Nature 520:702–705

    CAS  PubMed  Google Scholar 

  8. Zhou JH, Rossi J (2017) Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discov 16:181–202

    CAS  PubMed  Google Scholar 

  9. Guo YH, Chen JL, Cheng MP, Monchaud D, Zhou J, Ju HX (2017) A thermophilic tetramolecular G-quadruplex/hemin DNAzyme. Angew Chem Int Edit 56:16636–16640

    CAS  Google Scholar 

  10. Wittrup A, Lieberman J (2015) Knocking down disease: a progress report on siRNA therapeutics. Nat Rev Genet 16:543–552

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang YH, Miao L, Satterlee A, Huang L (2015) Delivery of oligonucleotides with lipid nanoparticles. Adv Drug Deliver Rev 87:68–80

    Google Scholar 

  12. Guo WW, Lu CH, Orbach R, Wang FA, Qi XJ, Cecconello A, Seliktar D, Willner I (2015) pH-stimulated DNA hydrogels exhibiting shape-memory properties. Adv Mater 27:73–78

    CAS  PubMed  Google Scholar 

  13. Ma DL, Zhang ZH, Wang MD, Lu LH, Zhong HJ, Leung CH (2015) Recent developments in G-quadruplex probes. Chem Biol 22:812–828

    CAS  PubMed  Google Scholar 

  14. Zhang S, Zou J, Elsabahy M, Karwa A, Li A, Moore DA, Dorshow RB, Wooley KL (2013) Poly(ethylene oxide)-block-polyphosphester-based paclitaxel conjugates as a platform for ultra-high paclitaxel-loaded multifunctional nanoparticles. Chem Sci 4:2122–2126

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Tao D, Feng C, Cui Y, Yang X, Manners I, Winnik MA, Huang X (2017) Monodisperse fiber-like micelles of controlled length and composition with an oligo(p-phenylenevinylene) core via “living” crystallization-driven self-assembly. J Am Chem Soc 139:7136–7139

    CAS  PubMed  Google Scholar 

  16. Lee K, Povlich LK, Kim J (2010) Recent advances in fluorescent and colorimetric conjugated polymer-based biosensors. Analyst 135:2179–2189

    CAS  PubMed  Google Scholar 

  17. Li K, Liu B (2012) Polymer encapsulated conjugated polymer nanoparticles for fluorescence bioimaging. J Mater Chem A 22:1257–1264

    CAS  Google Scholar 

  18. Meng Z, Hou W, Zhou H, Zhou L, Chen H, Wu C (2018) Therapeutic considerations and conjugated polymer-based photosensitizers for photodynamic therapy. Macromol Rapid Commun 39:1700614

    Google Scholar 

  19. Liu LZ, Chen H, Chen W, He F (2019) From binary to quaternary: high-tolerance of multi-acceptors enables development of efficient polymer solar cells. J Mater Chem A 7:7815–7822

    CAS  Google Scholar 

  20. Alemdaroglu FE, Herrmann A (2007) DNA meets synthetic polymers—highly versatile hybrid materials. Org Biomol Chem 5:1311–1320

    CAS  PubMed  Google Scholar 

  21. Kwak M, Herrmann A (2010) Nucleic acid/organic polymer hybrid materials: synthesis, superstructures, and applications. Angew Chem Int Edit 49:8574–8587

    CAS  Google Scholar 

  22. Kwak M, Herrmann A (2011) Nucleic acid amphiphiles: synthesis and self-assembled nanostructures. Chem Soc Rev 40:5745–5755

    CAS  PubMed  Google Scholar 

  23. Schnitzler T, Herrmann A (2012) DNA block copolymers: functional materials for nanoscience and biomedicine. Accounts Chem Res 45:1419–1430

    CAS  Google Scholar 

  24. Peterson AM, Heemstra JM (2015) Controlling self-assembly of DNA-polymer conjugates for applications in imaging and drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7:282–297

    CAS  PubMed  Google Scholar 

  25. Pan G, Jin X, Mou Q, Zhang C (2017) Recent progress on DNA block copolymer. Chinese Chem Lett 28:1822–1828

    CAS  Google Scholar 

  26. Zhao Z, Du T, Liang F, Liu S (2018) Amphiphilic DNA organic hybrids: functional materials in nanoscience and potential application in biomedicine. Int J Mol Sci 19:2283

    PubMed Central  Google Scholar 

  27. Lee K, Povlich LK, Kim J (2007) Label-free and self-signal amplifying molecular DNA sensors based on bioconjugated polyelectrolytes. Adv Funct Mater 17:2580–2587

    CAS  Google Scholar 

  28. Jia Y, Zuo X, Lou X, Miao M, Cheng Y, Min X, Li X, Xia F (2015) Rational designed bipolar, conjugated polymer-DNA composite beacon for the sensitive detection of proteins and ions. Anal Chem 87:3890–3894

    CAS  PubMed  Google Scholar 

  29. Zhao Y, Zheng C, Zhang L, Chen Y, Ye Y, Zhao M (2015) Knockdown of STAT3 expression in SKOV3 cells by biodegradable siRNA-PLGA/CSO conjugate micelles. Colloids Surf B Biointerfaces 127:155–163

    CAS  PubMed  Google Scholar 

  30. Lee SH, Mok H, Lee Y, Park TG (2011) Self-assembled siRNA–PLGA conjugate micelles for gene silencing. J Control Release 152:152–158

    CAS  PubMed  Google Scholar 

  31. Isoda K, Kanayama N, Fujita M, Takarada T, Maeda M (2013) DNA terminal mismatch-induced stabilization of polymer micelles from RAFT-generated poly(N-isopropylacrylamide)-DNA block copolymers. Chem-Asian J 8:3079–3084

    CAS  PubMed  Google Scholar 

  32. Sowwan M, Faroun M, Mentovich E, Ibrahim I, Haboush S, Alemdaroglu FE, Kwak M, Richter S, Herrmann A (2010) Polarizability of DNA block copolymer nanoparticles observed by electrostatic force microscopy. Macromol Rapid Commun 31:1242–1246

    CAS  PubMed  Google Scholar 

  33. Ni Q, Zhang F, Zhang Y, Zhu G, Wang Z, Teng Z, Wang C, Yung BC, Niu G, Lu G, Zhang L, Chen X (2018) In situ shRNA synthesis on DNA-polylactide nanoparticles to treat multidrug resistant breast cancer. Adv Mater 30:1705737

    Google Scholar 

  34. Wang D, Lu X, Jia F, Tan X, Sun X, Cao X, Wai F, Zhang C, Zhang K (2017) Precision tuning of DNA- and poly(ethylene glycol)-based nanoparticles via coassembly for effective antisense gene regulation. Chem Mater 29:9882–9886

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Li S, Schroeder CM (2018) Synthesis and direct observation of thermoresponsive DNA copolymers. ACS Macro Lett 7:281–286

    CAS  Google Scholar 

  36. Kubo T, Rumiana B, Ohba H, Fujii M (2003) Antisense effects of DNA-peptide conjugates. Nucleic acids symposium series, vol 1. Oxford University Press, Oxford, pp 179–180

    Google Scholar 

  37. Li C, Faulkner-Jones A, Dun AR, Jin J, Chen P, Xing Y, Yang Z, Li Z, Shu W, Liu D, Duncan RR (2015) Rapid formation of a supramolecular polypeptide-DNA hydrogel for in situ three-dimensional multilayer bioprinting. Angew Chem Int Edit 54:3957–3961

    CAS  Google Scholar 

  38. Jeong J (2003) A new antisense oligonucleotide delivery system based on self-assembled ODN–PEG hybrid conjugate micelles. J Control Release 93:183–191

    CAS  PubMed  Google Scholar 

  39. Yang L, Meng L, Zhang X, Chen Y, Zhu G, Liu H, Xiong X, Sefah K, Tan W (2011) Engineering polymeric aptamers for selective cytotoxicity. J Am Chem Soc 133:13380–13386

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu K, Zheng LF, Liu Q, de Vries JW, Gerasimov JY, Herrmann A (2014) Nucleic acid chemistry in the organic phase: from functionalized oligonucleotides to DNA side chain polymers. J Am Chem Soc 136:14255–14262

    CAS  PubMed  Google Scholar 

  41. Ding F, Mou Q, Ma Y, Pan G, Guo Y, Tong G, Choi CHJ, Zhu X, Zhang C (2018) A crosslinked nucleic acid nanogel for effective siRNA delivery and antitumor therapy. Angew Chem Int Edit 57:3064–3068

    CAS  Google Scholar 

  42. Talom RM, Fuks G, Kaps L, Oberdisse J, Cerclier C, Gaillard C, Mingotaud C, Gauffre F (2011) DNA-polymer micelles as nanoparticles with recognition ability. Chem-Eur J 17:13495–13501

    CAS  PubMed  Google Scholar 

  43. Mentovich ED, Livanov K, Prusty DK, Sowwan M, Richter S (2012) DNA-nanoparticle assemblies go organic: macroscopic polymeric materials with nanosized features. J Nanobiotechnol 10:21

    CAS  Google Scholar 

  44. Sun Y, Ji Y, Wang D, Wang J, Liu D (2018) Stabilization of an intermolecular i-motif by lipid modification of cytosine-oligodeoxynucleotides. Org Biomol Chem 16:4857–4863

    CAS  PubMed  Google Scholar 

  45. Alemdaroglu FE, Ding K, Berger R, Herrmann A (2006) DNA-templated synthesis in three dimensions: introducing a micellar scaffold for organic reactions. Angew Chem Int Edit 45:4206–4210

    CAS  Google Scholar 

  46. Kwak M, Gao J, Prusty DK, Musser AJ, Markov VA, Tombros N, Stuart MC, Browne WR, Boekema EJ, ten Brinke G, Jonkman HT, van Wees BJ, Loi MA, Herrmann A (2011) DNA block copolymer doing it all: from selection to self-assembly of semiconducting carbon nanotubes. Angew Chem Int Edit 50:3206–3210

    CAS  Google Scholar 

  47. Albert SK, Thelu HV, Golla M, Krishnan N, Chaudhary S, Varghese R (2014) Self-assembly of DNA-oligo(p-phenylene–ethynylene) hybrid amphiphiles into surface-engineered vesicles with enhanced emission. Angew Chem Int Edit 53:8352–8357

    CAS  Google Scholar 

  48. Jia F, Lu X, Tan X, Zhang K (2015) Facile synthesis of nucleic acid-polymer amphiphiles and their self-assembly. Chem Commun 51:7843–7846

    CAS  Google Scholar 

  49. Chien MP, Rush AM, Thompson MP, Gianneschi NC (2010) Programmable shape-shifting micelles. Angew Chem Int Edit 49:5076–5080

    CAS  Google Scholar 

  50. Luo Q, Shi Z, Zhang Y, Chen XJ, Han SY, Baumgart T, Chenoweth DM, Park SJ (2016) DNA island formation on binary block copolymer vesicles. J Am Chem Soc 138:10157–10162

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Yang CJ, Pinto M, Schanze K, Tan W (2005) Direct synthesis of an oligonucleotide-poly(phenylene ethynylene) conjugate with a precise one-to-one molecular ratio. Angew Chem Int Edit 44:2572–2576

    CAS  Google Scholar 

  52. Bousmail D, Chidchob P, Sleiman HF (2018) Cyanine-mediated DNA nanofiber growth with controlled dimensionality. J Am Chem Soc 140:9518–9530

    CAS  PubMed  Google Scholar 

  53. Edwardson TGW, Carneiro KMM, Serpell CJ, Sleiman HF (2014) An efficient and modular route to sequence-defined polymers appended to DNA. Angew Chem Int Edit 53:4567–4571

    CAS  Google Scholar 

  54. Averick SE, Dey SK, Grahacharya D, Matyjaszewski K, Das SR (2014) Solid-phase incorporation of an ATRP initiator for polymer-DNA biohybrids. Angew Chem Int Edit 53:2739–2744

    CAS  Google Scholar 

  55. Pan X, Lathwal S, Mack S, Yan J, Das SR, Matyjaszewski K (2017) Automated synthesis of well-defined polymers and biohybrids by atom transfer radical polymerization using a DNA synthesizer. Angew Chem Int Edit 56:2740–2743

    CAS  Google Scholar 

  56. Fu L, Wang Z, Lathwal S, Enciso AE, Simakova A, Das SR, Russell AJ, Matyjaszewski K (2018) Synthesis of polymer bioconjugates via photoinduced atom transfer radical polymerization under blue light irradiation. ACS Macro Lett 7:1248–1253

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lueckerath T, Strauch T, Koynov K, Barner-Kowollik C, Ng DYW, Weil T (2019) DNA-polymer conjugates by photoinduced RAFT polymerization. Biomacromol 20:212–221

    CAS  Google Scholar 

  58. Li F, Wang C, Guo W (2018) Multifunctional poly-N-isopropylacrylamide/DNAzyme microgels as highly efficient and recyclable catalysts for biosensing. Adv Funct Mater 28:1705876

    Google Scholar 

  59. Hu Y, Guo W, Kahn JS, Aleman-Garcia MA, Willner I (2016) A shape-memory DNA-based hydrogel exhibiting two internal memories. Angew Chem Int Edit 55:4210–4214

    CAS  Google Scholar 

  60. Cangialosi A, Yoon C, Liu J, Huang Q, Guo J, Nguyen TD, Gracias DH, Schulman RJS (2017) DNA sequence-directed shape change of photopatterned hydrogels via high-degree swelling. Science 357:1126–1130

    CAS  PubMed  Google Scholar 

  61. Zhang C, Hao L, Calabrese CM, Zhou Y, Choi CH, Xing H, Mirkin CA (2015) Biodegradable DNA-brush block copolymer spherical nucleic acids enable transfection agent-free intracellular gene regulation. Small 11:5360–5368

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Levenson EA, Kiick KL (2014) DNA-polymer conjugates for immune stimulation through Toll-like receptor 9 mediated pathways. Acta Biomater 10:1134–1145

    CAS  PubMed  Google Scholar 

  63. Roloff A, Nelles DA, Thompson MP, Yeo GW, Gianneschi NC (2018) Self-transfecting micellar RNA: modulating nanoparticle cell interactions via high density display of small molecule ligands on micelle coronas. Bioconjug Chem 29:126–135

    CAS  PubMed  Google Scholar 

  64. Roloff A, Carlini AS, Callmann CE, Gianneschi NC (2017) Micellar thrombin-binding aptamers: reversible nanoscale anticoagulants. J Am Chem Soc 139:16442–16445

    CAS  PubMed  Google Scholar 

  65. Rush AM, Nelles DA, Blum AP, Barnhill SA, Tatro ET, Yeo GW, Gianneschi NC (2014) Intracellular mRNA regulation with self-assembled locked nucleic acid polymer nanoparticles. J Am Chem Soc 136:7615–7618

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Rush AM, Thompson MP, Tatro ET, Gianneschi NC (2013) Nuclease-resistant DNA via high-density packing in polymeric Micellar Nanoparticle coronas. ACS Nano 7:1379–1387

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Jeong JH, Park TG (2001) Novel polymer–DNA hybrid polymeric micelles composed of hydrophobic poly(d, l-lactic-co-glycolic acid) and hydrophilic oligonucleotides. Bioconjug Chem 12:917–923

    CAS  PubMed  Google Scholar 

  68. Cutler JI, Auyeung E, Mirkin CA (2012) Spherical nucleic acids. J Am Chem Soc 134:1376–1391

    CAS  PubMed  Google Scholar 

  69. Li H, Zhang BH, Lu XG, Tan XY, Jia F, Xiao Y, Cheng ZH, Li Y, Silva DO, Schrekker HS, Zhang K, Mirkin CA (2018) Molecular spherical nucleic acids. Proc Natl Acad Sci USA 115:4340–4344

    CAS  PubMed  Google Scholar 

  70. Li Z, Zhang Y, Fullhart P, Mirkin CA (2004) Reversible and chemically programmable micelle assembly with DNA block-copolymer amphiphiles. Nano Lett 4:1055–1058

    CAS  Google Scholar 

  71. Chen XJ, Sanchez-Gaytan BL, Hayik SE, Fryd M, Wayland BB, Park SJ (2010) Self-assembled hybrid structures of DNA block-copolymers and nanoparticles with enhanced DNA binding properties. Small 6:2256–2260

    CAS  PubMed  Google Scholar 

  72. Kim CJ, Jeong EH, Lee H, Park SJ (2019) A dynamic DNA nanostructure with switchable and size-selective molecular recognition properties. Nanoscale 11:2501–2509

    CAS  PubMed  Google Scholar 

  73. Carneiro KMM, Hamblin GD, Hanni KD, Fakhoury J, Nayak MK, Rizis G, McLaughlin CK, Bazzi HS, Sleiman HF (2012) Stimuli-responsive organization of block copolymers on DNA nanotubes. Chem Sci 3:1980–1986

    CAS  Google Scholar 

  74. Alemdaroglu FE, Alemdaroglu NC, Langguth P, Herrmann A (2008) DNA block copolymer micelles—a combinatorial tool for cancer nanotechnology. Adv Mater 20:899–902

    CAS  Google Scholar 

  75. Alemdaroglu FE, Alemdaroglu NC, Langguth P, Herrmann A (2008) Cellular uptake of DNA block copolymer micelles with different shapes. Macromol Rapid Commun 29:326–329

    CAS  Google Scholar 

  76. Kwak M, Minten IJ, Anaya D-M, Musser AJ, Brasch M, Nolte RJM, Müllen K, Cornelissen JJLM, Herrmann A (2010) Virus-like particles templated by DNA Micelles: a general method for loading virus nanocarriers. J Am Chem Soc 132:7834–7835

    CAS  PubMed  Google Scholar 

  77. Rodriguez-Pulido A, Kondrachuk AI, Prusty DK, Gao J, Loi MA, Herrmann A (2013) Light-triggered sequence-specific cargo release from DNA block copolymer-lipid vesicles. Angew Chem Int Edit 52:1008–1012

    CAS  Google Scholar 

  78. Kwak M, Musser AJ, Lee J, Herrmann A (2010) DNA-functionalised blend micelles: mix and fix polymeric hybrid nanostructures. Chem Commun 46:4935–4937

    CAS  Google Scholar 

  79. Wu F, Zhao Z, Chen C, Cao T, Li C, Shao Y, Zhang Y, Qiu D, Shi Q, Fan QH, Liu D (2018) Self-collapsing of single molecular poly-propylene oxide (PPO) in a 3D DNA network. Small 14:1703426

    Google Scholar 

  80. Ding K, Alemdaroglu FE, Borsch M, Berger R, Herrmann A (2007) Engineering the structural properties of DNA block copolymer micelles by molecular recognition. Angew Chem Int Edit 46:1172–1175

    CAS  Google Scholar 

  81. Zhao Z, Wang L, Liu Y, Yang Z, He YM, Li Z, Fan QH, Liu D (2012) pH-induced morphology-shifting of DNA-b-poly(propylene oxide) assemblies. Chem Commun 48:9753–9755

    CAS  Google Scholar 

  82. Safak M, Alemdaroglu FE, Li Y, Ergen E, Herrmann A (2007) Polymerase chain reaction as an efficient tool for the preparation of block copolymers. Adv Mater 19:1499–1505

    CAS  Google Scholar 

  83. Alemdaroglu FE, Wang J, Borsch M, Berger R, Herrmann A (2008) Enzymatic control of the size of DNA block copolymer nanoparticles. Angew Chem Int Edit 47:974–976

    CAS  Google Scholar 

  84. Ayaz MS, Kwak M, Alemdaroglu FE, Wang J, Berger R, Herrmann A (2011) Synthesis of DNA block copolymers with extended nucleic acid segments by enzymatic ligation: cut and paste large hybrid architectures. Chem Commun 47:2243–2245

    CAS  Google Scholar 

  85. Sugawara Y, Tamaki T, Ohashi H, Yamaguchi T (2013) Control of the poly(N-isopropylacrylamide) phase transition via a single strand-double strand transformation of conjugated DNA. Soft Matter 9:3331–3340

    CAS  Google Scholar 

  86. Guo W, Lu CH, Qi XJ, Orbach R, Fadeev M, Yang HH, Willner I (2014) Switchable bifunctional stimuli-triggered poly-N-isopropylacrylamide/DNA hydrogels. Angew Chem Int Edit 53:10134–10138

    CAS  Google Scholar 

  87. Umeno D, Mori T, Maeda M (1998) Single stranded DNA-poly(N-isopropylacrylamide) conjugate for affinity precipitation separation of oligonucleotides. Chem Commun 20:1433–1434

    Google Scholar 

  88. Mori T, Umeno D, Maeda M (2001) Sequence-specific affinity precipitation of oligonucleotide using poly(N-isopropylacrylamide)-oligonucleotide conjugate. Biotechnol Bioeng 72:261–268

    CAS  PubMed  Google Scholar 

  89. Umeno D, Kawasaki M, Maeda M (1998) Water-soluble conjugate of double-stranded DNA and poly(N-isopropylacrylamide) for one-pot affinity precipitation separation of DNA-binding proteins. Bioconjug Chem 9:719–724

    CAS  PubMed  Google Scholar 

  90. Cavalieri F, Postma A, Lee L, Caruso F (2009) Assembly and functionalization of DNA–polymer microcapsules. ACS Nano 3:234–240

    CAS  PubMed  Google Scholar 

  91. Kim CJ, Hu X, Park SJ (2016) Multimodal shape transformation of dual-responsive DNA block copolymers. J Am Chem Soc 138:14941–14947

    CAS  PubMed  Google Scholar 

  92. Wilks TR, Bath J, de Vries JW, Raymond JE, Herrmann A, Turberfield AJ, O’Reilly RK (2013) “Giant surfactants” created by the fast and efficient functionalization of a DNA tetrahedron with a temperature-responsive polymer. ACS Nano 7:8561–8572

    CAS  PubMed  Google Scholar 

  93. Trinh T, Liao C, Toader V, Barlog M, Bazzi HS, Li J, Sleiman HF (2018) DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns. Nat Chem 10:184–192

    CAS  PubMed  Google Scholar 

  94. Serpell CJ, Edwardson TG, Chidchob P, Carneiro KM, Sleiman HF (2014) Precision polymers and 3D DNA nanostructures: emergent assemblies from new parameter space. J Am Chem Soc 136:15767–15774

    CAS  PubMed  Google Scholar 

  95. Chidchob P, Edwardson TG, Serpell CJ, Sleiman HF (2016) Synergy of two assembly languages in DNA nanostructures: self-assembly of sequence-defined polymers on DNA cages. J Am Chem Soc 138:4416–4425

    CAS  PubMed  Google Scholar 

  96. Trinh T, Chidchob P, Bazzi HS, Sleiman HF (2016) DNA micelles as nanoreactors: efficient DNA functionalization with hydrophobic organic molecules. Chem Commun 52:10914–10917

    CAS  Google Scholar 

  97. Bousmail D, Amrein L, Fakhoury JJ, Fakih HH, Hsu JCC, Panasci L, Sleiman HF (2017) Precision spherical nucleic acids for delivery of anticancer drugs. Chem Sci 8:6218–6229

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Rahbani JF, Vengut-Climent E, Chidchob P, Gidi Y, Trinh T, Cosa G, Sleiman HF (2018) DNA nanotubes with hydrophobic environments: toward new platforms for guest encapsulation and cellular delivery. Adv Healthc Mater 7:1701049

    Google Scholar 

  99. Fakhoury JJ, Edwardson TG, Conway JW, Trinh T, Khan F, Barłóg M, Bazzi HS, Sleiman HF (2015) Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown. Nanoscale 7:20625–20634

    CAS  PubMed  Google Scholar 

  100. Dore MD, Fakhoury JJ, Lacroix A, Sleiman HF (2018) Templated synthesis of spherical RNA nanoparticles with gene silencing activity. Chem Commun 54:11296–11299

    CAS  Google Scholar 

  101. Wu WB, Bazan GC, Liu B (2017) Conjugated-polymer-amplified sensing, imaging, and therapy. Chem-Us 2:760–790

    CAS  Google Scholar 

  102. Han L, Wang M, Jia X, Chen W, Qian H, He F (2018) Uniform two-dimensional square assemblies from conjugated block copolymers driven by π–π interactions with controllable sizes. Nat Commun 9:865

    PubMed  PubMed Central  Google Scholar 

  103. Kamps AC, Cativo MHM, Chen X-J, Park S-J (2014) Self-Assembly of DNA-coupled semiconducting block copolymers. Macromolecules 47:3720–3726

    CAS  Google Scholar 

  104. Knudsen JB, Liu L, Bank Kodal AL, Madsen M, Li Q, Song J, Woehrstein JB, Wickham SF, Strauss MT, Schueder F, Vinther J, Krissanaprasit A, Gudnason D, Smith AA, Ogaki R, Zelikin AN, Besenbacher F, Birkedal V, Yin P, Shih WM, Jungmann R, Dong M, Gothelf KV (2015) Routing of individual polymers in designed patterns. Nat Nanotechnol 10:892–898

    CAS  PubMed  Google Scholar 

  105. Yang T-HJRPoMS (2008) Recent applications of polyacrylamide as biomaterials. Recent Patents Mater Sci 1:29–40

    CAS  Google Scholar 

  106. Kang HZ, Trondoli AC, Zhu GZ, Chen Y, Chang YJ, Liu HP, Huang YF, Zhang XL, Tan WH (2011) Near-infrared light-responsive core-shell nanogels for targeted drug delivery. ACS Nano 5:5094–5099

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Ren J, Hu Y, Lu C-H, Guo W, Aleman-Garcia MA, Ricci F, Willner I (2015) pH-responsive and switchable triplex-based DNA hydrogels. Chem Sci 6:4190–4195

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Liao WC, Lilienthal S, Kahn JS, Riutin M, Sohn YS, Nechushtai R, Willner I (2017) pH- and ligand-induced release of loads from DNA-acrylamide hydrogel microcapsules. Chem Sci 8:3362–3373

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Sicilia G, Grainger-Boultby C, Francini N, Magnusson JP, Saeed AO, Fernández-Trillo F, Spain SG, Alexander C (2014) Programmable polymer–DNA hydrogels with dual input and multiscale responses. Biomater Sci 2:203–211

    CAS  Google Scholar 

  110. Lu CH, Guo W, Hu Y, Qi XJ, Willner I (2015) Multitriggered shape-memory acrylamide-DNA hydrogels. J Am Chem Soc 137:15723–15731

    CAS  PubMed  Google Scholar 

  111. Hu Y, Lu C-H, Guo W, Aleman-Garcia MA, Ren J, Willner I (2015) A shape memory acrylamide/DNA hydrogel exhibiting switchable dual pH-responsiveness. Adv Funct Mater 25:6867–6874

    CAS  Google Scholar 

  112. Sutthasupa S, Shiotsuki M, Sanda F (2010) Recent advances in ring-opening metathesis polymerization and application to synthesis of functional materials. Polym J 42:905–915

    CAS  Google Scholar 

  113. Lu X, Watts E, Jia F, Tan X, Zhang K (2014) Polycondensation of polymer brushes via DNA hybridization. J Am Chem Soc 136:10214–10217

    CAS  PubMed  Google Scholar 

  114. Tan X, Lu X, Jia F, Liu X, Sun Y, Logan JK, Zhang K (2016) Blurring the role of oligonucleotides: spherical nucleic acids as a drug delivery vehicle. J Am Chem Soc 138:10834–10837

    CAS  PubMed  Google Scholar 

  115. Gibbs JM, Park S-J, Anderson DR, Watson KJ, Mirkin CA, Nguyen ST (2005) Polymer–DNA hybrids as electrochemical probes for the detection of DNA. J Am Chem Soc 127:1170–1178

    CAS  PubMed  Google Scholar 

  116. Watson KJ, Park SJ, Im JH, Nguyen ST, Mirkin CA (2001) DNA-block copolymer conjugates. J Am Chem Soc 123:5592–5593

    CAS  PubMed  Google Scholar 

  117. Lu X, Tran TH, Jia F, Tan X, Davis S, Krishnan S, Amiji MM, Zhang K (2015) Providing oligonucleotides with steric selectivity by brush-polymer-assisted compaction. J Am Chem Soc 137:12466–12469

    CAS  PubMed  Google Scholar 

  118. Jia F, Lu X, Wang D, Cao X, Tan X, Lu H, Zhang K (2017) Depth-profiling the nuclease stability and the gene silencing efficacy of brush-architectured poly(ethylene glycol)-DNA conjugates. J Am Chem Soc 139:10605–10608

    CAS  PubMed  Google Scholar 

  119. Jia F, Lu X, Tan X, Wang D, Cao X, Zhang K (2017) Effect of PEG architecture on the hybridization thermodynamics and protein accessibility of PEGylated oligonucleotides. Angew Chem Int Edit 56:1239–1243

    CAS  Google Scholar 

  120. Lu X, Jia F, Tan X, Wang D, Cao X, Zheng J, Zhang K (2016) Effective antisense gene regulation via noncationic, polyethylene glycol brushes. J Am Chem Soc 138:9097–9100

    CAS  PubMed  Google Scholar 

  121. Matyjaszewski K (2018) Advanced materials by atom transfer radical polymerization. Adv Mater 30:1706441

    Google Scholar 

  122. Averick SE, Paredes E, Dey SK, Snyder KM, Tapinos N, Matyjaszewski K, Das SR (2013) Autotransfecting short interfering RNA through facile covalent polymer escorts. J Am Chem Soc 135:12508–12511

    CAS  PubMed  Google Scholar 

  123. Fouz MF, Mukumoto K, Averick S, Molinar O, McCartney BM, Matyjaszewski K, Armitage BA, Das SR (2015) Bright fluorescent nanotags from bottlebrush polymers with DNA-tipped bristles. ACS Cent Sci 1:431–438

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Fouz MF, Dey SK, Mukumoto K, Matyjaszewski K, Armitage BA, Das SR (2018) Accessibility of densely localized DNA on soft polymer nanoparticles. Langmuir 34:14731–14737

    CAS  PubMed  Google Scholar 

  125. Dong YC, Chen SB, Zhang SJ, Sodroski J, Yang ZQ, Liu DS, Mao YD (2018) Folding DNA into a lipid-conjugated nanobarrel for controlled reconstitution of membrane proteins. Angew Chem Int Edit 57:2072–2076

    CAS  Google Scholar 

  126. Averick S, Paredes E, Li W, Matyjaszewski K, Das SR (2011) Direct DNA conjugation to star polymers for controlled reversible assemblies. Bioconjug Chem 22:2030–2037

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge financial support by Grants from Shenzhen Fundamental Research Programs (no. JCYJ20160226193029593, JCYJ20170817105645935), Guangdong Innovative and Entrepreneurial Research Team Program (no. 2016ZT06G587), and the National Natural Science Foundation of China (no. 51503096).

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  1. Department of Materials Science and Engineering, Southern University of Science and Technology, 1088 Xueyuan Blvd, Nanshan District, Shenzhen, 518055, Guangdong, People’s Republic of China

    Fan Xiao, Zixiang Wei & Leilei Tian

  2. School of Materials Science and Engineering, Harbin Institute of Technology, Nangang District, Harbin, 150001, People’s Republic of China

    Fan Xiao

  3. Department of Chemistry, Western Washington University, 516 High Street, Bellingham, WA, 98225-9150, USA

    Maggie Wang, Alexandra Hoff & Ying Bao

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  1. Fan Xiao
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  2. Zixiang Wei
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  3. Maggie Wang
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This article is part of the Topical Collection “DNA Nanotechnology: From Structure to Functionality”; edited by Chunhai Fan, Yonggang Ke.

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Xiao, F., Wei, Z., Wang, M. et al. Oligonucleotide–Polymer Conjugates: From Molecular Basics to Practical Application. Top Curr Chem (Z) 378, 24 (2020). https://doi.org/10.1007/s41061-020-0286-8

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Keywords

  • Oligonucleotide–polymer conjugates
  • DNA block copolymers
  • Functional nucleic acid
  • Self-assembly
  • Drug delivery