Synthesis of Star Polymers by RAFT Polymerization as Versatile Nanoparticles for Biomedical Applications*
Jinming Hu A , Ruirui Qiao B , Michael R. Whittaker B , John F. Quinn B and Thomas P. Davis B C D
+ Author Affiliations
- Author Affiliations
A CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
B ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic. 3052, Australia.
C Chemistry Department, University of Warwick, Coventry CV4 7AL, UK.
D Corresponding author. Email: thomas.p.davis@monash.edu
Australian Journal of Chemistry 70(11) 1161-1170 https://doi.org/10.1071/CH17391
Submitted: 11 July 2017 Accepted: 18 August 2017 Published: 13 September 2017
Abstract
The precise control of polymer chain architecture has been made possible by developments in polymer synthesis and conjugation chemistry. In particular, the synthesis of polymers in which at least three linear polymeric chains (or arms) are tethered to a central core has yielded a useful category of branched architecture, so-called star polymers. Fabrication of star polymers has traditionally been achieved using either a core-first technique or an arm-first approach. Recently, the ability to couple polymeric chain precursors onto a functionalized core via highly efficient coupling chemistry has provided a powerful new methodology for star synthesis. Star syntheses can be implemented using any of the living polymerization techniques using ionic or living radical intermediates. Consequently, there are innumerable routes to fabricate star polymers with varying chemical composition and arm numbers. In comparison with their linear counterparts, star polymers have unique characteristics such as low viscosity in solution, prolonged blood circulation, and high accumulation in tumour regions. These advantages mean that, far beyond their traditional application as rheology control agents, star polymers may also be useful in the medical and pharmaceutical sciences. In this account, we discuss recent advances made in our laboratory focused on star polymer research ranging from improvements in synthesis through to novel applications of the product materials. Specifically, we examine the core-first and arm-first preparation of stars using reversible addition–fragmentation chain transfer (RAFT) polymerization. Further, we also discuss several biomedical applications of the resulting star polymers, particularly those made by the arm-first protocol. Emphasis is given to applications in the emerging area of nanomedicine, in particular to the use of star polymers for controlled delivery of chemotherapeutic agents, protein inhibitors, signalling molecules, and siRNA. Finally, we examine possible future developments for the technology and suggest the further work required to enable clinical applications of these interesting materials.
References
[1] C. Boyer, M. H. Stenzel, T. P. Davis, J. Polym. Sci. Part A: Polym. Chem. 2011, 49, 551.| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1ejur%2FF&md5=9fef1c5d64cf2acf5298faa82e7576ccCAS |
[2] B. S. Sumerlin, A. P. Vogt, Macromolecules 2010, 43, 1.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVensrrK&md5=32e0009344f2087a2d399f1e794ef02cCAS |
[3] L. J. Fetters, A. D. Kiss, D. S. Pearson, G. F. Quack, F. J. Vitus, Macromolecules 1993, 26, 647.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXotFOmtQ%3D%3D&md5=f74a1e6ee9800044eae1a4683a4153a1CAS |
[4] J. M. Ren, T. G. McKenzie, Q. Fu, E. H. H. Wong, J. T. Xu, Z. S. An, S. Shanmugam, T. P. Davis, C. Boyer, G. G. Qiao, Chem. Rev. 2016, 116, 6743.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XpsFOhsrw%3D&md5=d7153d926879f76418fb7072ba4ccb8bCAS |
[5] H. F. Gao, Macromol. Rapid Commun. 2012, 33, 722.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjvVWqu7g%3D&md5=9f9da0bccf22af05887a224c0cbdb243CAS |
[6] N. Hadjichristidis, H. Iatrou, M. Pitsikalis, J. Mays, Prog. Polym. Sci. 2006, 31, 1068.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1yktrvM&md5=482ad39ccdae5ec1815bbd37946d7f28CAS |
[7] M. Morton, S. D. Gadkary, T. E. Helminiak, F. Bueche, J. Polym. Sci., Polym. Phys. Ed. 1962, 57, 471.
| 1:CAS:528:DyaF38XktFWnu7Y%3D&md5=31d0c77b64ad1c5a3286751fea16ed88CAS |
[8] A. Blencowe, J. F. Tan, T. K. Goh, G. G. Qiao, Polymer 2009, 50, 5.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXksFyjsA%3D%3D&md5=4920df4a05182af206d5f7ac494e3e84CAS |
[9] H. Gao, K. Matyjaszewski, J. Am. Chem. Soc. 2007, 129, 11828.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpvVCntLY%3D&md5=e734deb835bc4485107e1bb89399813aCAS |
[10] M. R. Whittaker, M. J. Monteiro, Langmuir 2006, 22, 9746.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVKqsLbI&md5=0c8a2266bf2be54941d20b729d36cc9dCAS |
[11] Q. Zhang, L. Su, J. Collins, G. S. Chen, R. Wallis, D. A. Mitchell, D. M. Haddleton, C. R. Becer, J. Am. Chem. Soc. 2014, 136, 4325.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXjtVequr8%3D&md5=370bb24fd66c33373fed47ca3e45b261CAS |
[12] D. Kuckling, A. Wycisk, J. Polym. Sci. Part A: Polym. Chem. 2013, 51, 2980.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmt1Sqs7Y%3D&md5=77a1bfdc0677d01ede6857d83d630f74CAS |
[13] J. T. Wiltshire, G. G. Qiao, Aust. J. Chem. 2007, 60, 699.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFKgur7M&md5=23e108a4fbc3fac7cad819c7f311f4d1CAS |
[14] K. Khanna, S. Varshney, A. Kakkar, Polym. Chem. 2010, 1, 1171.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtl2msLrM&md5=1f09895459542e84f53a4a69bbbe4b25CAS |
[15] T. P. Le, G. Moad, E. Rizzardo, S. H. Thang, WO 1998001478 1998.
[16] M. Stenzel-Rosenbaum, T. P. Davis, V. Chen, A. G. Fane, J. Polym. Sci. Part A: Polym. Chem. 2001, 39, 2777.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlsFKlsbo%3D&md5=bffb8c82b25fe6054f334df2022bbcbdCAS |
[17] M. H. Stenzel, T. P. Davis, J. Polym. Sci. Part A: Polym. Chem. 2002, 40, 4498.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XptlahsLc%3D&md5=a4aa255a0bb61e74ed153e0b045cc11fCAS |
[18] M. H. Stenzel, T. P. Davis, C. Barner-Kowollik, Chem. Commun. 2004, 1546.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXltFWnsbY%3D&md5=c85b0f8564b5745cef187f2e0b1faeabCAS |
[19] J. Bernard, X. J. Hao, T. P. Davis, C. Barner-Kowollik, M. H. Stenzel, Biomacromolecules 2006, 7, 232.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht12rtbzP&md5=bd5d20a76c9035cf396477539ca6d383CAS |
[20] J. F. Quinn, R. P. Chaplin, T. P. Davis, J. Polym. Sci. Part A: Polym. Chem. 2002, 40, 2956.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xmt12hu7k%3D&md5=7851b436171bf91153d18c20dfe3bf4bCAS |
[21] X. J. Hao, C. Nilsson, M. Jesberger, M. H. Stenzel, E. Malmstrom, T. P. Davis, E. Östmark, C. Barner-Kowollik, J. Polym. Sci. Part A: Polym. Chem. 2004, 42, 5877.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVCjtLzL&md5=277eb26dcd3373185ad3cd2ef88c469fCAS |
[22] X. J. Hao, E. Malmstrom, T. P. Davis, M. H. Stenzel, C. Barner-Kowollik, Aust. J. Chem. 2005, 58, 483.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXltFymsb4%3D&md5=fc4007c02f394505fb0a7c9562d2692aCAS |
[23] E. Setijadi, L. Tao, J. Q. Liu, Z. F. Jia, C. Boyer, T. P. Davis, Biomacromolecules 2009, 10, 2699.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXpsFGisb0%3D&md5=8e0dd81cb56296da9d061f368cf0e854CAS |
[24] J. Q. Liu, H. Y. Liu, Z. F. Jia, V. Bulmus, T. P. Davis, Chem. Commun. 2008, 6582.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVKntb3M&md5=725ddc0b38685451d705ac5eb0f57f17CAS |
[25] J. Q. Liu, L. Tao, J. T. Xu, Z. F. Jia, C. Boyer, T. P. Davis, Polymer 2009, 50, 4455.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVOju7fJ&md5=008cab048d87c9d8dfa80724086d4a05CAS |
[26] C. Barner-Kowollik, T. P. Davis, M. H. Stenzel, Aust. J. Chem. 2006, 59, 719.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFeqsr%2FP&md5=3420dafc091a3656704565a47ffa712dCAS |
[27] H. T. Lord, J. F. Quinn, S. D. Angus, M. R. Whittaker, M. H. Stenzel, T. P. Davis, J. Mater. Chem. 2003, 13, 2819.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXotlyqtLg%3D&md5=7aeb23b8a4c7921ff90d963c3020ad05CAS |
[28] J. A. Syrett, D. M. Haddleton, M. R. Whittaker, T. P. Davis, C. Boyer, Chem. Commun. 2011, 1449.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXot1Crtw%3D%3D&md5=e74f3560e42827dc8f9d108400dd1075CAS |
[29] X. H. Wei, G. Moad, B. W. Muir, E. Rizzardo, J. Rosselgong, W. T. Yang, S. H. Thang, Macromol. Rapid Commun. 2014, 35, 840.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXitFarsL0%3D&md5=bb5e5496adfca03c33dd6d0c9d4a6430CAS |
[30] J. Ferreira, J. Syrett, M. Whittaker, D. Haddleton, T. P. Davis, C. Boyer, Polym. Chem. 2011, 2, 1671.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXpslKltL0%3D&md5=c03d622aad7ba82bd7b1a5809aca4938CAS |
[31] C. L. Zhang, M. Miao, X. T. Cao, Z. S. An, Polym. Chem. 2012, 3, 2656.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFansLnI&md5=9eb75c87a85ef131acefe533b2db86e4CAS |
[32] Q. Qiu, G. Y. Liu, Z. S. An, Chem. Commun. 2011, 12685.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsV2ktLjJ&md5=68a5413d0ff1c9b923f32797e68c9c66CAS |
[33] L. Zhang, K. Katapodi, T. P. Davis, C. Barner-Kowollik, M. H. Stenzel, J. Polym. Sci. Part A: Polym. Chem. 2006, 44, 2177.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtVeltLc%3D&md5=92dac22481d1d384d142f0326a31f082CAS |
[34] C. Boyer, M. Whittaker, T. P. Davis, J. Polym. Sci. Part A: Polym. Chem. 2011, 49, 5245.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1Gqs7fI&md5=8615744919c8d67806bd79f277aed7fdCAS |
[35] G. M. Soliman, A. Sharma, D. Maysinger, A. Kakkar, Chem. Commun. 2011, 9572.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVWgs73O&md5=7319add62dc6261330b50de48dd0a114CAS |
[36] J. N. Liu, H. E. Duong, M. R. Whittaker, T. P. Davis, C. Boyer, Macromol. Rapid Commun. 2012, 33, 760.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XlsFSqsLY%3D&md5=3b8b407f27d578ef3a2ce0955d24cd17CAS |
[37] S. J. Kim, D. M. Ramsey, C. Boyer, T. P. Davis, S. R. McAlpine, ACS Med. Chem. Lett. 2013, 4, 915.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtFOltrzE&md5=99fb52c86d8fea9099ebb459cdbee469CAS |
[38] Z. M. Wu, H. Liang, J. A. Lu, W. L. Deng, J. Polym. Sci. Part A: Polym. Chem. 2010, 48, 3323.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXotlWnsL0%3D&md5=f9303c8b50ef97cf38bf791ae61f9692CAS |
[39] Z. M. Wu, H. Liang, J. A. Lu, Macromolecules 2010, 43, 5699.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXms1Shtbc%3D&md5=501715853c2db53524da93e31cec865dCAS |
[40] H. T. T. Duong, K. Jung, S. K. Kutty, S. Agustina, N. N. M. Adnan, J. S. Basuki, N. Kumar, T. P. Davis, N. Barraud, C. Boyer, Biomacromolecules 2014, 15, 2583.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXpsVGgtbg%3D&md5=7b332dcecb7be887d34ff9f585bb47c9CAS |
[41] C. Boyer, J. Teo, P. Phillips, R. B. Erlich, S. Sagnella, G. Sharbeen, T. Dwarte, H. T. T. Duong, D. Goldstein, T. P. Davis, M. Kavallaris, J. McCarroll, Mol. Pharm. 2013, 10, 2435.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmt1yks7o%3D&md5=c28d4744cf354f44f08c60e892bb3874CAS |
[42] J. Teo, J. A. McCarroll, C. Boyer, J. Youkhana, S. M. Sagnella, H. T. T. Duong, J. Liu, G. Sharbeen, D. Goldstein, T. P. Davis, M. Kavallaris, P. A. Phillips, Biomacromolecules 2016, 17, 2337.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XpslOqsrk%3D&md5=3b63ec3904006b21ecd3e651154c70e8CAS |
[43] H. Y. Cho, A. Srinivasan, J. Hong, E. Hsu, S. G. Liu, A. Shrivats, D. Kwak, A. K. Bohaty, H.-j. Paik, J. O. Hollinger, K. Matyjaszewski, Biomacromolecules 2011, 12, 3478.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFWqt73K&md5=6adc99170a655b79bc0e610740dea9ebCAS |
[44] X. J. Li, Y. F. Qian, T. Liu, X. L. Hu, G. Y. Zhang, Y. Z. You, S. Y. Liu, Biomaterials 2011, 32, 6595.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXos1Sks7k%3D&md5=c7510acf7972ec7dde833ec16ede9ef1CAS |
[45] Y. M. Li, H. S. Yu, Y. F. Qian, J. M. Hu, S. Y. Liu, Adv. Mater. 2014, 26, 6734.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVSnurfO&md5=ff41c735f13bfeb6e288c9508d89e3d5CAS |
[46] Y. Li, Y. F. Qian, T. Liu, G. Y. Zhang, J. M. Hu, S. Y. Liu, Polym. Chem. 2014, 5, 1743.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhvFGiu70%3D&md5=5c35755ab2be59c6e2b8d8da4141efd9CAS |
[47] T. Liu, X. J. Li, Y. F. Qian, X. L. Hu, S. Y. Liu, Biomaterials 2012, 33, 2521.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XntFKrtQ%3D%3D&md5=c7db597322a0bf26edb8b31e44a3a09aCAS |
[48] Y. Li, M. Beija, S. Laurent, L. V. Elst, R. N. Muller, H. T. T. Duong, A. B. Lowe, T. P. Davis, C. Boyer, Macromolecules 2012, 45, 4196.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XmslKjtLc%3D&md5=8ee0a9cc141fb7ba74a92e6f123186bdCAS |
[49] Y. Li, S. Laurent, L. Esser, L. V. Elst, R. N. Muller, A. B. Lowe, C. Boyer, T. P. Davis, Polym. Chem. 2014, 5, 2592.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXjslGmsb8%3D&md5=8928abd8076041d30342de901a911ec3CAS |
[50] K. W. Wang, H. Peng, K. J. Thurecht, S. Puttick, A. K. Whittaker, Polym. Chem. 2014, 5, 1760.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhvFGiu7Y%3D&md5=a1489a2436af42741ca12b434f9e1912CAS |
[51] J. M. Hu, T. Liu, G. Y. Zhang, F. Jin, S. Y. Liu, Macromol. Rapid Commun. 2013, 34, 749.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhslKmsLvM&md5=b4f2993fccedc7364ef76eb88c5242f0CAS |
[52] F. Cheng, E. M. Bonder, A. Doshi, F. Jakle, Polym. Chem. 2012, 3, 596.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvFalurg%3D&md5=76fcd6053704f42a9afbe45a83d31b17CAS |
[53] C. T. Adkins, E. Harth, Macromolecules 2008, 41, 3472.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlt1GhsL0%3D&md5=1c82f7cbf030529f6b72f62e69378a9aCAS |
[54] K. M. Yang, H. Liang, J. Lu, J. Mater. Chem. 2011, 21, 10390.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXosVWgtL8%3D&md5=5d1abe9075ec2d3e8eb670efde8e97c7CAS |
[55] C. T. Adkins, J. N. Dobish, C. S. Brown, B. Mayrsohn, S. K. Hamilton, F. Udoji, K. Radford, T. E. Yankeelov, J. C. Gore, E. Harth, Polym. Chem. 2012, 3, 390.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XntlehsA%3D%3D&md5=3e53ce5a3ec25a0aea8b0bf2a7765ecaCAS |
[56] Y. Li, H. T. T. Duong, S. Laurent, A. MacMillan, R. M. Whan, L. V. Elst, R. N. Muller, J. Hu, A. Lowe, C. Boyer, T. P. Davis, Adv. Healthc. Mater. 2015, 4, 148.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXivFWjuw%3D%3D&md5=f2311635b038e9c4552aa8a650b54d65CAS |
[57] Y. Li, H. T. T. Duong, M. W. Jones, J. S. Basuki, J. M. Hu, C. Boyer, T. P. Davis, ACS Macro Lett. 2013, 2, 912.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsFWksLrM&md5=4cecd5c02ee21e020f40accfae0a964cCAS |
[58] S. Y. Khor, J. M. Hu, V. M. McLeod, J. F. Quinn, M. Williamson, C. J. H. Porter, M. R. Whittaker, L. M. Kaminskas, T. P. Davis, Nanomed.: Nanotechnol. Biol. Med. 2015, 11, 2099.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhsFSitb3O&md5=120bf24e055facab8851ca8717cf5d80CAS |
[59] S. Y. Khor, J. M. Hu, V. M. McLeod, J. F. Quinn, C. J. H. Porter, M. R. Whittaker, L. M. Kaminskas, T. P. Davis, J. Pharm. Sci. 2016, 105, 293.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhtF2mtr%2FF&md5=b3c608484c5f3c7b3f6cf933856dcf99CAS |
[60] J. J. Glass, Y. Li, R. De Rose, A. P. R. Johnston, E. I. Czuba, S. Y. Khor, J. F. Quinn, M. R. Whittaker, T. P. Davis, S. J. Kent, ACS Appl. Mater. Interfaces 2017, 9, 12182.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXkvVyisLg%3D&md5=b3e1945b961318946e41a68e45b74a0bCAS |
[61] T. G. McKenzie, Q. Fu, M. Uchiyama, K. Satoh, J. T. Xu, C. Boyer, M. Kamigaito, G. G. Qiao, Adv. Sci. 2016, 3, 1500394.
| Crossref | GoogleScholarGoogle Scholar |
[62] M. E. Fox, F. C. Szoka, J. M. J. Frechet, Acc. Chem. Res. 2009, 42, 1141.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnslSkt7o%3D&md5=2d514a2dedcf2527ff07421c9318460aCAS |
