화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.29, No.10, 665-680, October, 2021
DOI10.1007/s13233-021-9093-5  Export Citation
Systematic Combination of Oligonucleotides and Synthetic Polymers for Advanced Therapeutic Applications
Moohyun Han, Jiyun Beon, Ju Young Lee1, and Seung Soo Oh†
  • Department of Materials Science and Engineering, Pohang University of Science Technology (POSTECH), Pohang, Gyeongbuk 37673, Korea
  • 1Research Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT), Ulsan 44429, Korea
E-mail:
The potential of oligonucleotides is exceptional in therapeutics because of their high safety, potency, and specificity compared to conventional therapeutic agents. However, many obstacles, such as low in vivo stability and poor cellular uptake, have hampered their clinical success. Use of polymeric carriers can be an effective approach for overcoming the biological barriers and thereby maximizing the therapeutic efficacy of the oligonucleotides due to the availability of highly tunable synthesis and functional modification of various polymers. As loaded in the polymeric carriers, the therapeutic oligonucleotides, such as antisense oligonucleotides, small interfering RNAs, microRNAs, and even messenger RNAs, become nuclease-resistant by bypassing renal filtration and can be efficiently internalized into disease cells. In this review, we introduced a variety of systematic combinations between the therapeutic oligonucleotides and the synthetic polymers, including the uses of highly functionalized polymers responding to a wide range of endogenous and exogenous stimuli for spatiotemporal control of oligonucleotide release. We also presented intriguing characteristics of oligonucleotides suitable for targeted therapy and immunotherapy, which can be fully supported by versatile polymeric carriers.
Keywords:nucleic acid;gene delivery;polymeric carrier;stimuli-responsive system;immunotherapy
  1. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D, Cell, 181, 281 (2020)
  2. Wallace DC, Annu. Rev. Genet., 39, 359 (2005)
  3. Blauwkamp TA, Thair S, Rosen MJ, et al., Nat. Microbiol., 4, 663 (2019)
  4. Chapman SJ, Hill AVS, Nat. Rev. Genet., 13, 175 (2012)
  5. Stephenson ML, Zamecnik PC, Proc. Natl. Acad. Sci., 75, 285 (1978)
  6. Nishiyama N, Kataoka K, Pharmacol. Ther., 112, 630 (2006)
  7. Tsui NB, Ng EK, Lo YD, Clin. Chem., 48, 1647 (2002)
  8. Iversen F, Yang C, Dagnæs-Hansen F, Schaffert DH, Kjems J, GaoS, Theranostics, 3, 201 (2013)
  9. Panyam J, Labhasetwar V, Adv. Drug Deliv. Rev., 55, 329 (2003)
  10. Cabral H, Miyata K, Osada K, Kataoka K, Chem. Rev., 118(14), 6844 (2018)
  11. Roberts TC, Langer R, Wood MJA, Nat. Rev. Drug Dis., 19, 673 (2020)
  12. Luther DC, Huang R, Jeon T, Zhang X, Lee YW, Nagaraj H, Rotello VM, Adv. Drug Deliv. Rev., 156, 188 (2020)
  13. Cutler JI, Auyeung E, Mirkin CA, J. Am. Chem. Soc., 134(3), 1376 (2012)
  14. Thambi T, Li Y, Lee DS, J. Control. Release, 267, 57 (2017)
  15. Park H, Lee KY, Lee SJ, Park KE, Park WH, Macromol. Res., 15(3), 238 (2007)
  16. Ashraf S, Park HK, Park H, Lee SH, Macromol. Res., 24(4), 297 (2016)
  17. Kumari A, Yadav SK, Yadav SC, Colloids Surf. B: Biointerfaces, 75, 1 (2010)
  18. Alfei S, Castellaro S, Macromol. Res., 25(12), 1172 (2017)
  19. Kim JH, Oh YT, Lee KS, Yun JM, Park BT, Oh KT, Macromol. Res., 19(5), 453 (2011)
  20. Wang C, Ravi S, Martinez GV, Chinnasamy V, Raulji P, Howell M, Davis Y, Mallela J, Seehra MS, Mohapatra S, J. Control. Release, 163, 82 (2012)
  21. Zhang HJ, Zhao X, Cheng LJ, Yang CX, Yan XP, Talanta, 219 (2020)
  22. Verma IM, Somia N, Nature, 389(6648), 239 (1997)
  23. Boussif O, Lezoualc'H F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP, Proc. Natl. Acad. Sci., 92
  24. Carthew RW, Sontheimer EJ, Cell, 136, 642 (2009)
  25. Esquela-Kerscher A, Slack FJ, Nat. Rev. Cancer, 6, 259 (2006)
  26. Hill AB, Chen M, Chen CK, Pfeifer BA, Jones CH, Trends Biotechnol., 34, 91 (2016)
  27. Yoo H, Jo H, Oh SS, Mater. Adv., 1, 2663 (2020)
  28. Liu JW, Cao ZH, Lu Y, Chem. Rev., 109(5), 1948 (2009)
  29. Ellington AD, Szostak JW, Nature, 346, 818 (1990)
  30. Park SV, Yang JS, Jo H, Kang B, Oh SS, Jung GY, Biotechnol. Adv., 37, 107452 (2019)
  31. Willner I, Shlyahovsky B, Zayats M, Willner B, Chem. Soc. Rev., 37, 1153 (2008)
  32. Kim T, Nam K, Kim YM, Yang K, Roh YH, ACS Nano, 15, 1942 (2021)
  33. Mintzer MA, Simanek EE, Chem. Rev., 109(2), 259 (2009)
  34. Danhier F, Feron O, Preat V, J. Control. Release, 148, 135 (2010)
  35. Kessenbrock K, Plaks V, Werb Z, Cell, 141, 52 (2010)
  36. Park G, Kang B, Park SV, Lee D, Seung, Nucleic Acids Res., 49, 4919 (2021)
  37. Setten RL, Rossi JJ, Han SP, Nat. Rev. Drug Discov., 18, 421 (2019)
  38. Tsui NBY, Ng EKO, Lo YMD, Clin. Chem., 48, 1647 (2002)
  39. Kawabata K, Takakura Y, Hashida M, Pharm. Res., 12, 825 (1995)
  40. Moret I, Peris JE, Guillem VM, Benet M, Revert F, Das F, Crespo A, Alino SF, J. Control. Release, 76, 169 (2001)
  41. Cho KC, Choi SH, Park TG, Macromol. Res., 14(3), 348 (2006)
  42. Benjaminsen RV, Mattebjerg MA, Henriksen JR, Moghimi SM, Andresen TL, Mol. Ther., 21, 149 (2013)
  43. Creixell M, Peppas NA, Nano Today, 7(4), 367 (2012)
  44. Krishnamachari Y, Salem AK, Adv. Drug Deliv. Rev., 61, 205 (2009)
  45. Jung H, Kim SA, Lee E, Mok H, Macromol. Res., 23(5), 449 (2015)
  46. Kang L, Gao Z, Huang W, Jin M, Wang Q, Acta Pharm. Sin. B, 5, 169 (2015)
  47. Krieg AM, Nat. Rev. Drug Discov., 5, 471 (2006)
  48. Li N, Zhao L, Qi L, Li Z, Luan Y, Prog. Polym. Sci, 58, 1 (2016)
  49. Wang Y, Gao SJ, Ye WH, Yoon HS, Yang YY, Nat. Mater., 5(10), 791 (2006)
  50. Sun M, Wang K, Oupicky D, Adv. Healthc. Mater., 7, 170107 (2018)
  51. Gao Y, Wei M, Li X, Xu W, Ahiabu A, Perdiz J, Liu Z, Serpe M, Macromol. Res., 25(6), 513 (2017)
  52. Gerweck LE, Seetharaman K, Cancer Res., 56, 1194 (1996)
  53. Wang F, Lu CH, Willner I, Chem. Rev., 114(5), 2881 (2014)
  54. Kang B, Park SV, Soh HT, Oh SS, ACS Sens., 4, 2802 (2019)
  55. Cho M, Oh SS, Nie J, Stewart R, Eisenstein M, Chambers J, Marth JD, Walker F, Thomson JA, Soh HT, Proc. Natl. Acad. Sci., 110, 18460 (2013)
  56. Keefe AD, Pai S, Ellington A, Nat. Rev. Drug Discov., 9, 537 (2010)
  57. Zhuang YY, Deng HP, Su Y, He L, Wang RB, Tong GS, He DN, Zhu XY, Biomacromolecules, 17(6), 2050 (2016)
  58. Maruyama A, Adv. Drug Deliv. Rev., 52, 227 (2001)
  59. Kwak M, Herrmann A, Angew. Chem.-Int. Edit., 49, 8574 (2010)
  60. Hammond SM, Aartsma-Rus A, Alves S, et al., EMBO Mol. Med., 13 (2021)
  61. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG, Nat. Rev. Genet., 15, 541 (2014)
  62. Lachelt U, Wagner E, Chem. Rev., 115(19), 11043 (2015)
  63. Dowdy SF, Nat. Biotechnol., 35, 222 (2017)
  64. Piotrowski-Daspit AS, Kauffman AC, Bracaglia LG, Saltzman WM, Adv. Drug Deliv. Rev., 156, 119 (2020)
  65. Zamecnik PC, Stephenson ML, Proc. Natl. Acad. Sci., 75, 280 (1978)
  66. Watts JK, Corey DR, J. Pathol., 226, 365 (2012)
  67. Bennett CF, Annu. Rev. Med., 70, 307 (2019)
  68. Chirila TV, Rakoczy PE, Garrett KL, Lou X, Constable IJ, Biomaterials, 23, 321 (2002)
  69. Juliano RL, Nucleic Acids Res., 44, 6518 (2016)
  70. Merdan T, KopecEk J, Kissel T, Adv. Drug Deliv. Rev., 54, 715 (2002)
  71. Fattal E, Barratt G, Br. J. Pharmacol., 157, 179 (2009)
  72. De Rosa G, Quaglia F, Bochot A, Ungaro F, Fattal E, Biomacromolecules, 4(3), 529 (2003)
  73. Dheur S, Dias N, Van Aerschot A, et al., Antisense Nucleic Acid Drug Dev., 9, 515 (1999).
  74. Falzarano MS, Passarelli C, Ferlini A, Nucleic Acid Ther., 24, 87 (2014)
  75. Akhtar S, Hughes MD, Khan A, Bibby M, Hussain M, Nawaz Q, Double J, Sayyed P, Adv. Drug Deliv. Rev., 44, 3 (2000)
  76. Jain RA, Biomaterials, 21, 2475 (2000)
  77. Lewis KJ, Irwin WJ, Akhtar S, J. Drug Target., 5, 291 (1998)
  78. Dorsett Y, Tuschl T, Nat. Rev. Drug Discov., 3, 318 (2004)
  79. Whitehead KA, Langer R, Anderson DG, Nat. Rev. Drug Discov., 8, 129 (2009)
  80. Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, Malvy C, Biochem. Biophys. Res. Commun., 296(4), 1000 (2002)
  81. Kim DH, Rossi JJ, Nat. Rev. Genet., 8, 173 (2007)
  82. Tatiparti K, Sau S, Kashaw S, Iyer A, Nanomaterials, 7, 77 (2017)
  83. Alexis F, Pridgen E, Molnar LK, Farokhzad OC, Mol. Pharm., 5, 505 (2008)
  84. Mao S, Neu M, Germershaus O, Merkel O, Sitterberg J, Bakowsky U, Kissel T, Bioconjug. Chem., 17, 1209 (2006)
  85. Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, Wagner E, Mol. Ther., 11, 418 (2005)
  86. Jeong JH, Christensen LV, Yockman JW, Zhong Z, Engbersen JFJ, Kim WJ, Feijen J, Kim SW, Biomaterials, 28, 1912 (2007)
  87. Lam JKW, Chow MYT, Zhang Y, Leung SWS, Mol. Ther. Nucleic Acids, 4, e252 (2015)
  88. Friedman RC, Farh KKH, Burge CB, Bartel DP, Genome Res., 19, 92 (2008)
  89. Calin GA, Sevignani C, Dumitru CD, et al., Proc. Natl. Acad. Sci., 101, 2999 (2004)
  90. Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y, Adv. Drug Deliv. Rev., 81, 142 (2015)
  91. Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A, Cancer Res., 71, 5214 (2011)
  92. Kowalski PS, Rudra A, Miao L, Anderson DG, Mol. Ther., 27, 710 (2019)
  93. Lorenz C, Fotin-Mleczek M, Roth G, Becker C, Dam TC, Verdurmen WPR, Brock R, Probst J, Schlake T, RNA Biol., 8, 627 (2011)
  94. Cheng C, Convertine AJ, Stayton PS, Bryers JD, Biomaterials, 33, 6868 (2012)
  95. Wang Y, Zhang Z, Luo J, Han X, Wei Y, Wei X, Mol. Cancer, 20 (2021)
  96. Yin H, Kauffman KJ, Anderson DG, Nat. Rev. Drug Discov., 16, 387 (2017)
  97. Palmiero UC, Kaczmarek JC, Fenton OS, Anderson DG, Adv. Healthc. Mater., 7, 180024 (2018)
  98. Cordeiro RA, Serra A, Coelho JFJ, Faneca H, J. Control. Release, 310, 155 (2019)
  99. Patton JS, Byron PR, Nat. Rev. Drug Discov., 6, 67 (2007)
  100. Densmore CL, Orson FM, Xu B, Kinsey BM, Waldrep JC, Hua P, Bhogal B, Knight V, Mol. Ther., 1, 180 (2000)
  101. Patel AK, Kaczmarek JC, Bose S, Kauffman KJ, Mir F, Heartlein MW, Derosa F, Langer R, Anderson DG, Adv. Mater., 31, 180511 (2019)
  102. Jiang Y, Gaudin A, Zhang J, Agarwal T, Song E, Kauffman AC, Tietjen GT, Wang Y, Jiang Z, Cheng CJ, Saltzman WM, Biomaterials, 176, 122 (2018)
  103. Zhou JB, Liu J, Cheng CJ, Patel TR, Weller CE, Piepmeier JM, Jiang ZZ, Saltzman WM, Nat. Mater., 11(1), 82 (2012)
  104. Li Y, Gao J, Zhang C, Cao Z, Cheng D, Liu J, Shuai X, Top. Curr. Chem., 375, 27 (2017)
  105. Bus T, Traeger A, Schubert US, J. Mater. Chem. B, 6, 6904 (2018)
  106. Takemoto H, Miyata K, Nishiyama N, Kataoka K, Adv. Genet., 88, 289 (2014)
  107. Liu J, Huang Y, Kumar A, Tan A, Jin S, Mozhi A, Liang XJ, Biotechnol. Adv., 32, 693 (2014)
  108. Hu YB, Dammer EB, Ren RJ, Wang G, Transl. Neurodegener., 4 (2015)
  109. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM, Adv. Drug Deliv. Rev., 99, 28 (2016)
  110. Xu CF, Zhang HB, Sun CY, Liu Y, Shen S, Yang XZ, Zhu YH, Wang J, Biomaterials, 88, 48 (2016)
  111. Degors IMS, Wang C, Rehman ZU, Zuhorn IS, Accounts Chem. Res., 52, 1750 (2019)
  112. Itaka K, Ishii T, Hasegawa Y, Kataoka K, Biomaterials, 31, 3707 (2010)
  113. Nelson CE, Kim AJ, Adolph EJ, Gupta MK, Yu F, Hocking KM, Davidson JM, Guelcher SA, Duvall CL, Adv. Mater., 26(4), 607 (2014)
  114. Mi P, Theranostics, 10, 4557 (2020)
  115. Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z, J. Control. Release, 152, 2 (2011)
  116. Gerald, Tamas, Cell, 163, 560 (2015)
  117. Chang Y, Yang K, Wei P, Huang S, Pei Y, Zhao W, Pei Z, Angew. Chem.-Int. Edit., 53, 13126 (2014)
  118. Ganta S, Devalapally H, Shahiwala A, Amiji M, J. Control. Release, 126, 187 (2008)
  119. Choi S, Lee KD, J. Control. Release, 131, 70 (2008)
  120. Kam NWS, Liu Z, Dai HJ, J. Am. Chem. Soc., 127(36), 12492 (2005)
  121. Matsumoto S, Christie RJ, Nishiyama N, Miyata K, Ishii A, Oba M, Koyama H, Yamasaki Y, Kataoka K, Biomacromolecules, 10(1), 119 (2009)
  122. Jiang HL, Islam MA, Xing L, Firdous J, Cao W, He YJ, Zhu Y, Cho KH, Li HS, Cho CS, Top. Curr. Chem., 375, 34 (2017)
  123. Peng Q, Zhong Z, Zhuo R, Bioconjug. Chem., 19, 499 (2008)
  124. Li YL, Maciel D, Rodrigues J, Shi XY, Tomas H, Chem. Rev., 115(16), 8564 (2015)
  125. Nam K, Park JW, Bark H, Han J, Nah JW, Jang MK, Kim SW, Macromol. Res., 22(4), 370 (2014)
  126. Kawagishi H, Finkel T, Nat. Med., 20, 711 (2014)
  127. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB, Antioxid. Redox Signal., 20, 1126 (2014)
  128. Burgoyne JB, Oka SI, Ale-Agha N, Eaton P, Antioxid. Redox Signal., 18, 1042 (2013)
  129. Shim MS, Xia Y, Angew. Chem.-Int. Edit., 52, 6926 (2013)
  130. Wilson DS, Dalmasso G, Wang L, Sitaraman SV, Merlin D, Murthy N, Nat. Mater., 9, 923 (2010)
  131. Xu X, Saw PE, Tao W, Li Y, Ji X, Bhasin S, Liu Y, Ayyash D, Rasmussen J, Huo M, Shi J, Farokhzad OC, Adv. Mater., 29, 170014 (2017)
  132. Li Y, Bai H, Wang H, Shen Y, Tang G, Ping Y, Nanoscale, 10, 203 (2018)
  133. De La Rica R, Aili D, Stevens MM, Adv. Drug Deliv. Rev., 64, 967 (2012)
  134. Hu J, Zhang G, Liu S, Chem. Soc. Rev., 41, 5933 (2012)
  135. Yingyuad P, Mevel M, Prata C, Furegati S, Kontogiorgis C, Thanou M, Miller AD, Bioconjug. Chem., 24, 343 (2013)
  136. Wang C, Chen Q, Wang Z, Zhang X, Angew. Chem.-Int. Edit., 49, 8612 (2010)
  137. Hu Q, Katti PS, Gu Z, Nanoscale, 6, 12273 (2014)
  138. Wang HX, Yang XZ, Sun CY, Mao CQ, Zhu YH, Wang J, Biomaterials, 35, 7622 (2014)
  139. Bergers G, Brekken R, McMahon G, et al., Nat. Cell Biol., 2, 737 (2000)
  140. Yong VW, Power C, Forsyth P, Edwards DR, Nat. Rev. Neurosci., 2, 502 (2001)
  141. Qiu NS, Liu XR, Zhong Y, Zhou ZX, Piao Y, Miao L, Zhang QZ, Tang JB, Huang L, Shen YQ, Adv. Mater., 28(48), 10613 (2016)
  142. Raza A, Hayat U, Rasheed T, Bilal M, Iqbal HMN, J. Mater. Res. Technol., 8, 1497 (2019)
  143. Kono K, Ozawa T, Yoshida T, Ozaki F, Ishizaka Y, Maruyama K, Kojima C, Harada A, Aoshima S, Biomaterials, 31, 7096 (2010)
  144. Karino T, Koga S, Maeta M, Jpn. J. Surg., 18, 276 (1988)
  145. Song CW, Park HJ, Lee CK, Griffin R, Int. J. Hyperth, 21, 761 (2005)
  146. Kong G, Anyarambhatla G, Petros WP, Braun RD, Colvin OM, Needham D, Dewhirst MW, Cancer Res., 60, 6950 (2000)
  147. Lindner LH, Eichhorn ME, Eibl H, Teichert N, Schmitt-Sody M, Issels RD, Dellian M, Clin. Cancer Res., 10, 2168 (2004)
  148. Twaites BR, De Las Heras Alarcon C, Lavigne M, Saulnier A, Pennadam SS, Cunliffe D, Gorecki DC, Alexander C, J. Control. Release, 108, 472 (2005)
  149. Roy D, Brooks WLA, Sumerlin BS, Chem. Soc. Rev., 42, 7214 (2013)
  150. Pasparakis G, Tsitsilianis C, Polymer, 211, 123146 (2020)
  151. Haq MA, Su Y, Wang D, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 70, 842 (2017)
  152. Seo JW, Shin US, Macromol. Res., 23(11), 1073 (2015)
  153. Zintchenko A, Ogris M, Wagner E, Bioconjug. Chem., 17, 766 (2006)
  154. Schwerdt A, Zintchenko A, Concia M, Roesen N, Fisher K, Lindner LH, Issels R, Wagner E, Ogris M, Hum. Gene Ther., 19, 1283 (2008)
  155. Cao P, Sun X, Liang Y, Gao X, Li X, Li W, Song Z, Li W, Liang G, Nanomedicine, 10, 1585 (2015)
  156. Hernot S, Klibanov AL, Adv. Drug Deliv. Rev., 60, 1153 (2008)
  157. Ferrara K, Pollard R, Borden M, Annu. Rev. Biomed. Eng., 9, 415 (2007)
  158. Shapiro G, Wong AW, Bez M, et al., J. Control. Release, 223, 157 (2016)
  159. Meng FH, Zhong ZY, Feijen J, Biomacromolecules, 10(2), 197 (2009)
  160. Yan ND, Keller W, Scully NM, Lean DR, Dillon PJ, Nature, 381(6578), 141 (1996)
  161. Ash C, Dubec M, Donne K, Bashford T, Lasers Med. Sci., 32, 1909 (2017)
  162. Liu G, Liu W, Dong CM, Polym. Chem, 4, 3431 (2013)
  163. Shin J, Sung J, Kang M, et al., Proc. Natl. Acad. Sci., 116, 5973 (2019)
  164. Park JY, Umashankar M, Huh DS, Macromol. Res., 24(4), 350 (2016)
  165. Li Y, Yang J, Sun L, Wang W, Liu W, J. Mater. Chem. B, 2, 3868 (2014)
  166. Duan S, Cao D, Li X, Zhu H, Lan M, Tan Z, Song Z, Zhu R, Yin L, Chen Y, Biomaterials Science, 8, 290 (2020)
  167. Deng X, Zheng N, Song Z, Yin L, Cheng J, Biomaterials, 35, 5006 (2014)
  168. Nalluri SKM, Voskuhl J, Bultema JB, Boekema EJ, Ravoo BJ, Angew. Chem.-Int. Edit., 50, 9747 (2011)
  169. Shim MS, Kwon YJ, Adv. Drug Deliv. Rev., 64, 1046 (2012)
  170. Shubayev VI, Pisanic TR, Jin S, Adv. Drug Deliv. Rev., 61, 467 (2009)
  171. Lo YL, Chou HL, Liao ZX, et al., Nanoscale, 7, 8554 (2015)
  172. Han X, Xu K, Taratula O, Farsad K, Nanoscale, 11, 799 (2019)
  173. Park T, Jeong J, Kim S, Adv. Drug Deliv. Rev., 58, 467 (2006)
  174. Brannon-Peppas L, Blanchette JO, Adv. Drug Deliv. Rev., 56, 1649 (2004)
  175. Chiu SJ, Ueno NT, Lee RJ, J. Control. Release, 97, 357 (2004)
  176. Mitra A, Mulholland J, Nan A, McNeill E, Ghandehari H, Line BR, J. Control. Release, 102, 191 (2005)
  177. Yang L, Sun H, Liu Y, Hou W, Yang Y, Cai R, Cui C, Zhang P, Pan X, Li X, Li L, Sumerlin S, Tan W, Angew. Chem.-Int. Edit., 130, 17294 (2018)
  178. Mignani S, Shi X, Cena V, Majoral JP, Drug Discov. Today, 25, 1065 (2020)
  179. Oh SS, Lee BF, Leibfarth FA, Eisenstein M, Robb MJ, Lynd NA, Hawker CJ, Soh HT, J. Am. Chem. Soc., 136, 1510 (2014)
  180. Alibolandi M, Taghdisi SM, Ramezani P, Shamili FH, Farzad SA, Abnous K, Ramezani M, Int. J. Pharm., 519, 352 (2017)
  181. Sanmamed MF, Chen L, Cell, 175, 313 (2018)
  182. Xing L, Zhou TJ, Fan YT, He YJ, Pang T, Cho KH, Lu JJ, Jiang HL, Cho CS, Macromol. Res., 27(3), 215 (2019)
  183. June CH, O'Connor RS, Kawalekar OU, Ghassemi S, Milone MC, Science, 359(6382), 1361 (2018)
  184. Vollmer J, Krieg AM, Adv. Drug Deliv. Rev., 61, 195 (2009)
  185. Kumar M, Keller B, Makalou N, Sutton RE, Hum. Gene Ther., 12, 1893 (2001)
  186. Olden BR, Cheng Y, Yu JL, Pun SH, J. Control. Release, 282, 140 (2018)
  187. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A, Cell, 168, 707 (2017)
  188. June CH, Sadelain M, N. Engl. J. Med., 379, 64 (2018)
  189. Wilson JT, Keller S, Manganiello MJ, Cheng C, Lee CC, Opara C, Convertine A, Stayton PS, ACS Nano, 7, 3912 (2013)
  190. Kundu A, Nandi S, Nandi AK, Prog. Mater. Sci., 88, 136 (2017)
  191. Mi Y, Hagan CT, Vincent BG, Wang AZ, Adv. Sci., 6, 180184 (2019)
  192. Lv H, Zhang S, Wang B, Cui S, Yan J, J. Control. Release, 114, 100 (2006)
  193. Duncan R, Vicent MJ, Adv. Drug Deliv. Rev., 65, 60 (2013)