Abstract
We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly(ethylene oxide), poly(L-lysine), and poly(ɛ-caprolactone) arms, PEO(-b-PLL)-b-PCL, and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors, PEO(-b-PZLL)-b-PCL, were synthesized at first via the combination of consecutive “click” reactions and ring-opening polymerizations (ROP), where PZLL is poly(ɛ-benzyloxycarbonyl-L-lysine). Subsequently, the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers, PEO(-b-PLL)-b-PCL. In aqueous media at pH 7.4, PEO(-b-PLL)-b-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug, paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA (pDNA) at N/P ratios higher than ca. 2. Thus, PEO(-b-PLL)-b-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore, polyplexes of pDNA with paclitaxel-loaded PEO(-b-PLL)-b-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting, imaging, and diagnostics.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
Deming, T.J., Adv. Mater., 1997, 9: 299
Trzcinska, R., Szweda, D., Rangelov, S., Suder, P., Silberring, J., Dworak, A. and Trzebicka, B., J. Polym. Sci., Part A Polym. Chem., 2012, 50: 3104
Zhu, M.Q., Xiang, L., Yang, K., Shen, L.J., Long, F., Fan, J.B., Yi, H.Q., Xiang, J. and Aldred, M.P., J. Polym. Res., 2012, 19: 9808
Zhang, S.S., Chen, C.Y. and Li, Z.B., Chinese J. Polym. Sci., 2013, 31(2): 201
Li, H.B., Tian, Z., Zhang, A.Y. and Feng, Z.G., Chinese J. Polym. Sci., 2009, 27(3): 317
Gebhardt, K.E., Ahn, S., Venkatachalam, G. and Savin, D.A., J. Colloid Interface Sci., 2008, 317: 70
Li, C.H., Ge, Z.S., Fang, J. and Liu, S.Y., Macromolecules, 2009, 42: 2916
Xu, X.H., Li, C.X., Li, H.P., Liu, R., Jiang, C., Wu, Y., He, B. and Gu, Z.W., Sci. Chin. Chem., 2011, 54: 326
Cho, C.S., Cheon, J.B., Jeong, Y.I., Kim, I.S., Kim, S.H. and Akaike, T., Macromol. Rapid Commun., 1997, 18: 361
Babin, J., Rodriguez-Hernandez, J., Lecommandoux, S., Klok, H.A. and Achard, M.F., Faraday Discuss., 2005, 128: 179
Dimitrov, I. and Schlaad, H., Chem. Commun., 2003, 2944
Lubbert, A., Castelletto, V., Hamley, I.W., Nuhn, H., Scholl, M., Bourdillon, L., Wandrey, C. and Klok, H.A., Langmuir, 2005, 21: 6582
Checot, F., Rodriguez-Hernandez, J., Gnanou, Y. and Lecommandoux, S., Polym. Adv. Technol., 2006, 17: 782
Schlaad, H., Smarsly, B. and Below, I., Macromolecules, 2006, 39: 4631
Checot, F., Rodriguez-Hernandez, J., Gnanou, Y. and Lecommandoux, S., Biomol. Eng., 2007, 24: 81
Gil, G.O., Losik, M., Schlaad, H., Drechsler, M. and Hellweg, T., Langmuir, 2008, 24: 12823
Sun, J., Chen, X.S., Deng, C., Yu, H.J., Xie, Z.G. and Jing, X.B., Langmuir, 2007, 23: 8308
Sun, J., Deng, C., Chen, X.S., Yu, H.J., Tian, H.Y., Sun, J.R. and Jing, X.B., Biomacromolecules, 2007, 8: 1013
Kricheldorf, H.R. and Hauser, K., Biomacromolecules, 2001, 2: 1110
Caillol, S., Lecommandoux, S., Mingotaud, A.F., Schappacher, M., Soum, A., Bryson, N. and Meyrueix, R., Macromolecules, 2003, 36: 1118
Rong, G.Z., Deng, M.X., Deng, C., Tang, Z.H., Piao, L.H., Chen, X.S. and Jing, X.B., Biomacromolecules, 2003, 4: 1800
Sun, J., Chen, X.S., Lu, T.C., Liu, S., Tian, H.Y., Guo, Z.P. and Jing, X.B., Langmuir, 2008, 24: 10099
Holowka, E.P., Pochan, D.J. and Deming, T.J., J. Am. Chem. Soc., 2005, 127: 12423
Rodriguez-Hernandez, J. and Lecommandoux, S., J. Am. Chem. Soc., 2005, 127: 2026
Rao, J.Y., Luo, Z.F., Ge, Z.S., Liu, H. and Liu, S.Y., Biomacromolecules, 2007, 8: 3871
Zhang, X.Q., Li, J.G., Li, W. and Zhang, A., Biomacromolecules, 2007, 8: 3557
Pitsikalis, M., Pispas, S., Mays, J.W. and Hadjichristidis, N., Adv. Polym. Sci., 1998, 135: 1
Babin, J., Leroy, C., Lecommandoux, S., Borsali, R., Gnanou, Y. and Taton, D., Chem. Commun., 2005, 1993
Abraham, S., Ha, C.S. and Kim, I., J. Polym. Sci., Part A Polym. Chem., 2006, 44: 2774
Babin, J., Taton, D., Brinkmann, M. and Lecommandoux, S., Macromolecules, 2008, 41: 1384
Rao, J.Y., Zhang, Y.F., Zhang, J.Y. and Liu, S.Y., Biomacromolecules, 2008, 9: 2586
Li, Z.B., Kesselman, E., Talmon, Y., Hillmyer, M.A. and Lodge, T.P., Science, 2004, 306: 98
Li, Z.B., Hillmyer, M.A. and Lodge, T.P., Nano Lett., 2006, 6: 1245
Li, Z.B., Hillmyer, M.A. and Lodge, T.P., Langmuir, 2006, 22: 9409
Zhang, Y.F., Liu, H., Dong, H.F., Li, C.H. and Liu, S.Y., J. Polym. Sci., Part A Polym. Chem., 2009, 47: 1636
Zhang, W.D., Zhang, W., Zhang, Z.B., Cheng, Z.P., Tu, Y.F., Qiu, Y.S. and Zhu, X.L., J. Polym. Sci., Part A Polym. Chem., 2010, 48: 4268
Du, J., Sun, Y., Shi, Q.S., Liu, P.F., Zhu, M.J., Wang, C.H., Du, L.F. and Duan, Y.R., Int. J. Mol. Sci., 2012, 13: 516
Zhou, D.Z., Li, C.X., Hu, Y.L., Zhou, H., Chen, J.T., Zhang, Z.P. and Guo, T.Y., J. Mater. Chem., 2012, 22: 10743
Mintzer, M.A. and Simanek, E.E., Chem. Rev., 2009, 109: 259
Meng, F.H., Hennink, W.E. and Zhong, Z., Biomaterials, 2009, 30: 2180
Janat-Amsbury, M.M., Yockman, J.W., Lee, M., Kern, S., Furgeson, D.Y., Bikram, M. and Kim, S.W., Mol. Ther., 2004, 9: 829
Yue, X.Y., Qiao, Y., Qiao, N., Guo, S.T., Xing, J.F., Deng, L.D., Xu, J.Q. and Dong, A.J., Biomacromolecules, 2010, 11: 2306
Lu, X., Wang, Q.Q., Xu, F.J., Tang, G.P. and Yang, W.T., Biomaterials, 2011, 32: 4849
Sun, T.M., Du, J.Z., Yao, Y.D., Mao, C.Q., Dou, S., Huang, S.Y., Zhang, P.Z., Leong, K.W., Song, E.W. and Wang, J., Acs Nano, 2011, 5: 1483
Xiong, X.B. and Lavasanifar, A., Acs Nano, 2011, 5: 5202
Wang, Y., Gao, S.J., Ye, W.H., Yoon, H.S. and Yang, Y.Y., Nat. Mater., 2006, 5: 791
Qiu, L.Y. and Bae, Y.H., Biomaterials, 2007, 28: 4132
Guo, S.T., Qiao, Y., Wang, W.W., He, H.Y., Deng, L.D., Xing, J.F., Xu, J.Q., Liang, X.J. and Dong, A.J., J. Mater. Chem., 2010, 20: 6935
Bromberg, L. and Levin, G., Bioconjugate Chem., 1998, 9: 40
Wu, P., Feldman, A.K., Nugent, A.K., Hawker, C.J., Scheel, A., Voit, B., Pyun, J., Frechet, J.M.J., Sharpless, K.B. and Fokin, V.V., Angew. Chem., Int. Ed., 2004, 43: 3928
Lewis, W.G., Magallon, F.G., Fokin, V.V. and Finn, M.G., J. Am. Chem. Soc., 2004, 126: 9152
Altintas, O., Hizal, G. and Tunca, U., J. Polym. Sci., Part A Polym. Chem., 2006, 44: 5699
Kolb, H.C., Finn, M.G. and Sharpless, K.B., Angew. Chem., Int. Ed., 2001, 40: 2004
Qin, A.J., Lam, J.W.Y. and Tang, B.Z., Macromolecules, 2010, 43: 8693
Fu, R. and Fu, G.D., Polym. Chem., 2011, 2: 465
Agut, W., Taton, D. and Lecommandoux, S., Macromolecules, 2007, 40: 5653
Agut, W., Agnaou, R., Lecommandoux, S. and Taton, D., Macromol. Rapid Commun., 2008, 29: 1147
Wang, K., Liang, L.Y., Lin, S.L. and He, X.H., Eur. Polym. J., 2008, 44: 3370
Liu, T., Qian, Y.F., Hu, X.L., Ge, Z.S. and Liu, S.Y., J. Mater. Chem., 2012, 22: 5020
Li, X.J., Qian, Y.F., Liu, T., Hu, X.L., Zhang, G.Y., You, Y.Z. and Liu, S.Y., Biomaterials, 2011, 32: 6595
Zhu, C.H., Jung, S., Luo, S.B., Meng, F.H., Zhu, X.L., Park, T.G. and Zhong, Z.Y., Biomaterials, 2010, 31: 2408
Yue, Y.A., Jin, F., Deng, R., Cai, J.G., Chen, Y.C., Lin, M.C.M., Kung, H.F. and Wu, C., J. Controlled Release, 2011, 155: 67
Author information
Authors and Affiliations
Corresponding author
Additional information
Invited paper dedicated to Professor Fosong Wang on the occasion of his 80th birthday
Electronic Supplementary Material Supplementary material is available in the online version of this article at http//dx.doi.org/10.1007/s10118-013-1281-0.
The work was financially supported by the National Natural Science Foundation of China (Nos. 21274137, 91027026 and 51033005), Fundamental Research Funds for the Central Universities, and Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP, 20123402130010).
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Liu, T., Zhang, Yf. & Liu, Sy. Drug and plasmid DNA co-delivery nanocarriers based on abctype polypeptide hybrid miktoarm star copolymers. Chin J Polym Sci 31, 924–937 (2013). https://doi.org/10.1007/s10118-013-1281-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10118-013-1281-0