Citation: Wen-liang Wang, Xiao-jing Ma, Xi-fei Yu. pH-responsive Polymersome Based on PMCP-b-PDPA as a Drug Delivery System to Enhance Cellular Internalization and Intracellular Drug Release[J]. Chinese Journal of Polymer Science, ;2017, 35(11): 1352-1362. doi: 10.1007/s10118-017-1982-x shu

pH-responsive Polymersome Based on PMCP-b-PDPA as a Drug Delivery System to Enhance Cellular Internalization and Intracellular Drug Release

Wen-liang Wang ^a,b ,
Xiao-jing Ma ^a,, ,
Xi-fei Yu ^a,b,,

a.
The Polymer Composites Engineering Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
b.
University of Science and Technology of China, Hefei 230026, China

Corresponding author: Xiao-jing Ma, xjma@ciac.ac.cn Xi-fei Yu, xfyu@ciac.ac.cn
Received Date: 31 March 2017
Revised Date: 13 May 2017
Accepted Date: 17 May 2017

Fund Project: the National Natural Science Foundation of China 21603214the National Natural Science Foundation of China 21674109the National Natural Science Foundation of China 21304096the National Natural Science Foundation of China 21474103

Choline phosphate (CP) as a novel zwitterion possesses specific and excellent properties compared with phosphorylcholine (PC), as well as its polymer, such as poly(2-(methacryloyloxy)ethyl choline phosphate) (PMCP), has been studied extensively due to its unique characteristics of rapid cellular internalization via the special quadrupole interactions with the cell membrane. Recently, we reported a novel PMCP-based drug delivery system to enhance the cellular internalization where the drug was conjugated to the polymer via reversible acylhydrazone bond. Herein, to make full use of this feature of PMCP, we synthesized the diblock copolymer poly(2-(methacryloyloxy)ethyl choline phosphate)-b-poly(2-(diisopropylamino)ethyl methacrylate) (PMCP-b-PDPA), which could self-assemble into polymersomes with hydrophilic PMCP corona and hydrophobic membrane wall in mild conditions when the pH value is ≥ 6.4. It has been found that these polymersomes can be successfully used to load anticancer drug Dox with the loading content of about 11.30 wt%. After the polymersome is rapidly internalized by the cell with the aid of PMCP, the loaded drug can be burst-released in endosomes since PDPA segment is protonated at low pH environment, which renders PDPA to transfer from hydrophobic to hydrophilic, and the subsequent polymersomes collapse thoroughly. Ultimately, the "proton sponge" effect of PDPA chain can further accelerate the Dox to escape from endosome to cytoplasm to exert cytostatic effects. Meanwhile, the cell viability assays showed that the Dox-loaded polymersomes exhibited significant inhibitory effect on tumor cells, indicating its great potential as a targeted intracellular delivery system with high efficiency.
- Drug delivery,
- Choline phosphate,
- Polymersome,
- PDPA,
- Enhanced cellular internalization
1. [1]
  Chen, X., Parelkar, S.S., Henchey, E., Schneider, S. and Emrick, T., Bioconjugate Chem., 2012, 23:1753 doi: 10.1021/bc200667s
2. [2]
  Wang, H., Xu, F., Li, D., Liu, X., Jin, Q. and Ji, J., Polym. Chem., 2013, 4:2004 doi: 10.1039/c2py20981k
3. [3]
  Goda, T., Goto, Y. and Shihara, K., Biomaterials, 2010, 31:2380 doi: 10.1016/j.biomaterials.2009.11.095
4. [4]
  Morimoto, N., Wakamura, M., Muramatsu, K., Toita, S., Nakayama, M., Shoji, W., Suzuki, M. and Winnik, F.M., Biomacromolecules, 2016, 17:1523 doi: 10.1021/acs.biomac.6b00172
5. [5]
  Chen, S.F., Zheng, J., Li, L.Y. and Jiang, S.Y., J. Am. Chem. Soc., 2005, 127:14473 doi: 10.1021/ja054169u
6. [6]
  Schlenoff, J.B., Langmuir, 2014, 30:9625 doi: 10.1021/la500057j
7. [7]
  Chen, S., Yuan, L., Li, Q., Li, J., Zhu, X., Jiang, Y., Sha, O., Yang, X., Xin, J.H., Wang, J., Stadler, F.J. and Huang, P., Small, 2016, 12:3516 doi: 10.1002/smll.201600587
8. [8]
  Hu, G. and Emrick, T., J. Am. Chem. Soc., 2016, 138:1828 doi: 10.1021/jacs.5b13156
9. [9]
  Hu, G., Parelkar, S.S. and Emrick, T., Polym. Chem., 2015, 6:525 doi: 10.1039/C4PY01292E
10. [10]
  Morozova, S., Hu, G. and Emrick, A.T., ACS Macro Lett., 2016, 5:118 doi: 10.1021/acsmacrolett.5b00876
11. [11]
  Wang, F. and Liu, J., J. Am. Chem. Soc., 2015, 137:11736 doi: 10.1021/jacs.5b06642
12. [12]
  Perttu, E.K., Kohli, A.G. and Szoka, F.C., J. Am. Chem. Soc., 2012, 134:4485 doi: 10.1021/ja210989h
13. [13]
  Motion, J.P.M., Nguyen, J. and Szoka, F.C., Angew. Chem. Int. Ed., 2012, 51:9047 doi: 10.1002/anie.201204198
14. [14]
  Yu, X., Zou, Y., Horte, S., Janzen, J., Kizhakkedathu, J.N. and Brooks, D.E., Biomacromolecules, 2013, 14:2611 doi: 10.1021/bm400466e
15. [15]
  Yu, X., Yang, X., Horte, S., Kizhakkedathu, J.N. and Brooks, D.E., Biomaterials, 2014, 35:278 doi: 10.1016/j.biomaterials.2013.09.052
16. [16]
  Yu, X., Yang, X., Horte, S., Kizhakkedathu, J.N. and Brooks, D.E., Macromol. Biosci., 2014, 14:334 doi: 10.1002/mabi.201300425
17. [17]
  Yu, X., Yang, X., Horte, S., Kizhakkedathu, J.N. and Brooks, D.E., Chem. Commun., 2013, 49:6831 doi: 10.1039/c3cc41895b
18. [18]
  Yu, X., Liu, Z., Janzen, J., Chafeeva, I., Horte, S., Chen, W., Kainthan, R.K., Kizhakkedathu, J.N. and Brooks, D.E., Nat. Mater., 2012, 11:468 doi: 10.1038/nmat3272
19. [19]
  Chen, X., Chen, T., Lin, Z., Li, X., Wu, W. and Li, J., Chem. Commun., 2015, 51:487 doi: 10.1039/C4CC08681C
20. [20]
  Wang, W., Wang, B., Ma, X., Liu, S., Shang, X. and Yu, X., Biomacromolecules, 2016, 17:2223 doi: 10.1021/acs.biomac.6b00455
21. [21]
  Wang, W., Wang, B., Ma, X., Liu, S., Shang, X. and Yu, X., ACS Appl. Mater. Interfaces, 2017, DOI:10.1021/acsami.7b03317 doi: 10.1021/acsami.7b03317
22. [22]
  Meng, F., Zhong, Z. and Feijen, J., Biomacromolecules, 2009, 10:197 doi: 10.1021/bm801127d
23. [23]
  Pramod, P.S., Takamura, K., Chaphekar, S., Balasubramanian, N. and Jayakannan, M., Biomacromolecules, 2012, 13:3627 doi: 10.1021/bm301583s
24. [24]
  Robertson, J.D., Yealland, G., Avila-Olias, M., Chierico, L., Bandmann, O., Renshaw, S.A. and Battaglia, G., ACS Nano, 2014, 8:4650 doi: 10.1021/nn5004088
25. [25]
  Jia, L., Cui, D., Bignon, J., di Cicco, A., Wdzieczak-Bakala, J., Liu, J. and Li, M.H., Biomacromolecules, 2014, 15:2206 doi: 10.1021/bm5003569
26. [26]
  Liu, Z., Dong, C., Wang, X., Wang, H., Li, W., Tan, J. and Chang, J., ACS Appl. Mater. Interfaces, 2014, 6:2393 doi: 10.1021/am404734c
27. [27]
  Sun, H., Meng, F., Cheng, R., Deng, C. and Zhong, Z., Acta Biomater., 2014, 10:2159 doi: 10.1016/j.actbio.2014.01.010
28. [28]
  Wang, C., Yuan, Q., Yang, S. and Xu, J., Chinese J. Polym. Sci., 2015, 33:661 doi: 10.1007/s10118-015-1618-y
29. [29]
  Wang, M., Wang, T., Yuan, K. and Du, J. Chinese J. Polym. Sci., 2016, 34:44 doi: 10.1007/s10118-016-1725-4
30. [30]
  Yan, Q., Yuan, J., Cai, Z., Xin, Y., Kang, Y. and Yin, Y., J. Am. Chem. Soc., 2010, 132:9268 doi: 10.1021/ja1027502
31. [31]
  Wong, C.K., Laos, A.J., Soeriyadi, A.H., Wiedenmann, J., Curmi, P.M., Gooding, J.J., Marquis, C.P., Stenzel, M.H. and Thordarson, P., Angew. Chem. Int. Ed., 2015, 54:5317 doi: 10.1002/anie.201412406
32. [32]
  Du, J.Z. and Armes, S.P., J. Am. Chem. Soc., 2005, 127:12800 doi: 10.1021/ja054755n
33. [33]
  Yu, H., Zou, Y., Wang, Y., Huang, X., Huang, G., Sumer, B.D., Boothman, D.A. and Gao, J., ACS Nano, 2011, 11:9246
34. [34]
  Pearson, R.T., Warren, N.J., Lewis, A.L., Armes, S.P. and Battaglia, G., Macromolecules, 2013, 46:1400 doi: 10.1021/ma302228m
35. [35]
  Shen, L., Du, J., Steven, P.A. and Liu, S., Langmuir, 2008, 24:10019 doi: 10.1021/la801190z
36. [36]
  Chen, Y., Cheng, D., Chen, J., Wang, L. and Shuai, X., Small, 2014, 10:2678 doi: 10.1002/smll.v10.13
37. [37]
  Lomas, H., Du, J., Canton, I., Madsen, J., Warren, N., Armes, S.P., Lewis, A.L. and Battaglia, G., Macromol. Biosci., 2010, 10:513 doi: 10.1002/mabi.v10:5
38. [38]
  Zhang, J., Wu, L., Meng, F., Wang, Z., Deng, C., Liu, H. and Zhong, Z., Langmuir, 2012, 28:2056 doi: 10.1021/la203843m
39. [39]
  Jäger, A., Jäger, E., Surman, F., Höcherl, A., Angelov, B., Ulbrich, K., Drechsler, M., Garamus, V.M., Rodriguez-Emmenegger, C., Nallet, F. and Štěpánek, P., Polym. Chem., 2015, 6:4946 doi: 10.1039/C5PY00567A
40. [40]
  Du, J., Fan, L. and Liu, Q., Macromolecules, 2012, 45:8275 doi: 10.1021/ma3015728
41. [41]
  Giacomelli, C., Men, L.L. and Borsali, R., Biomacromolecules, 2006, 7:817 doi: 10.1021/bm0508921
1. [1]
  Jiaqi Huang , Renjiang Kong , Yanmei Li , Ni Yan , Yeyang Wu , Ziwen Qiu , Zhenming Lu , Xiaona Rao , Shiying Li , Hong Cheng . Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs. Chinese Chemical Letters, 2024, 35(8): 109254-. doi: 10.1016/j.cclet.2023.109254
2. [2]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
3. [3]
  Zhilong Xie , Guohui Zhang , Ya Meng , Yefei Tong , Jian Deng , Honghui Li , Qingqing Ma , Shisong Han , Wenjun Ni . A natural nano-platform: Advances in drug delivery system with recombinant high-density lipoprotein. Chinese Chemical Letters, 2024, 35(11): 109584-. doi: 10.1016/j.cclet.2024.109584
4. [4]
  Xingqun Pu , Rongrong Liu , Yuting Xie , Chenjing Yang , Jingyi Chen , Baoling Guo , Chun-Xia Zhao , Peng Zhao , Jian Ruan , Fangfu Ye , David A Weitz , Dong Chen . One-step preparation of biocompatible amphiphilic dimer nanoparticles with tunable particle morphology and surface property for interface stabilization and drug delivery. Chinese Chemical Letters, 2025, 36(3): 109820-. doi: 10.1016/j.cclet.2024.109820
5. [5]
  Makhloufi Zoulikha , Zhongjian Chen , Jun Wu , Wei He . Approved delivery strategies for biopharmaceuticals. Chinese Chemical Letters, 2025, 36(2): 110225-. doi: 10.1016/j.cclet.2024.110225
6. [6]
  Jing Zhang , Charles Wang , Yaoyao Zhang , Haining Xia , Yujuan Wang , Kun Ma , Junfeng Wang . Application of magnetotactic bacteria as engineering microrobots: Higher delivery efficiency of antitumor medicine. Chinese Chemical Letters, 2024, 35(10): 109420-. doi: 10.1016/j.cclet.2023.109420
7. [7]
  Tong Tong , Lezong Chen , Siying Wu , Zhong Cao , Yuanbin Song , Jun Wu . Establishment of a leucine-based poly(ester amide)s library with self-anticancer effect as nano-drug carrier for colorectal cancer treatment. Chinese Chemical Letters, 2024, 35(12): 109689-. doi: 10.1016/j.cclet.2024.109689
8. [8]
  Lihang Wang , Mary Li Javier , Chunshan Luo , Tingsheng Lu , Shudan Yao , Bing Qiu , Yun Wang , Yunfeng Lin . Research advances of tetrahedral framework nucleic acid-based systems in biomedicine. Chinese Chemical Letters, 2024, 35(11): 109591-. doi: 10.1016/j.cclet.2024.109591
9. [9]
  Yong-Dan Zhao , Yidan Wang , Rongrong Wang , Lina Chen , Hengtong Zuo , Xi Wang , Jihong Qiang , Geng Wang , Qingxia Li , Canqi Ping , Shuqiu Zhang , Hao Wang . Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH. Chinese Chemical Letters, 2024, 35(6): 108929-. doi: 10.1016/j.cclet.2023.108929
10. [10]
  Keyang Li , Yanan Wang , Yatao Xu , Guohua Shi , Sixian Wei , Xue Zhang , Baomei Zhang , Qiang Jia , Huanhua Xu , Liangmin Yu , Jun Wu , Zhiyu He . Flash nanocomplexation (FNC): A new microvolume mixing method for nanomedicine formulation. Chinese Chemical Letters, 2024, 35(10): 109511-. doi: 10.1016/j.cclet.2024.109511
11. [11]
  Yuanzheng Wang , Chen Zhang , Shuyan Han , Xiaoli Kong , Changyun Quan , Jun Wu , Wei Zhang . Cancer cell membrane camouflaged biomimetic gelatin-based nanogel for tumor inhibition. Chinese Chemical Letters, 2024, 35(11): 109578-. doi: 10.1016/j.cclet.2024.109578
12. [12]
  Yinglan Yu , Sajid Hussain , Jianping Qi , Lei Luo , Xuemei Zhang . Mechanisms and applications: Cargos transport to basolateral membranes in polarized epithelial cells. Chinese Chemical Letters, 2024, 35(12): 109673-. doi: 10.1016/j.cclet.2024.109673
13. [13]
  Han Wu , Yumei Wang , Zekai Ren , Hailin Cong , Youqing Shen , Bing Yu . The nanocarrier strategy for crossing the blood-brain barrier in glioma therapy. Chinese Chemical Letters, 2025, 36(4): 109996-. doi: 10.1016/j.cclet.2024.109996
14. [14]
  Yi Cao , Xiaojiao Ge , Yuanyuan Wei , Lulu He , Aiguo Wu , Juan Li . Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition. Chinese Chemical Letters, 2024, 35(4): 108672-. doi: 10.1016/j.cclet.2023.108672
15. [15]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
16. [16]
  Yujie Li , Ya-Nan Wang , Yin-Gen Luo , Hongcai Yang , Jinrui Ren , Xiao Li . Advances in synthetic biology-based drug delivery systems for disease treatment. Chinese Chemical Letters, 2024, 35(11): 109576-. doi: 10.1016/j.cclet.2024.109576
17. [17]
  Wenjun Yang , Qiaoling Tan , Wenjiao Xie , Xiaoyu Pan , Youyong Yuan . Construction and Characterization of Calcium Alginate Microparticle Drug Delivery System: A Novel Design and Teaching Practice in Polymer Experiments. University Chemistry, 2025, 40(3): 371-380. doi: 10.12461/PKU.DXHX202405150
18. [18]
  Ningyue Xu , Jun Wang , Lei Liu , Changyang Gong . Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy: A review of recent advances. Chinese Chemical Letters, 2024, 35(8): 109225-. doi: 10.1016/j.cclet.2023.109225
19. [19]
  Jiechen Liu , Xiaoguang Li , Ruiyang Xia , Yuqi Wang , Fenghe Zhang , Yongzhi Pang , Qing Li . Efficient suppression of oral squamous cell carcinoma through spatial dimension conversion drug delivery systems-enabled immunomodulatory-photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109619-. doi: 10.1016/j.cclet.2024.109619
20. [20]
  Chengde Wang , Liping Huang , Shanshan Wang , Lihao Wu , Yi Wang , Jun Dong . A distinction of gliomas at cellular and tissue level by surface-enhanced Raman scattering spectroscopy. Chinese Chemical Letters, 2024, 35(5): 109383-. doi: 10.1016/j.cclet.2023.109383

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(841)
HTML views(24)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142