Citation: Yuyao Liao, Zhen Fan, Jianzhong Du. Photocrosslinking-Immobilized Polymer Vesicles for Lowering Temperature Triggered Drug Release[J]. Acta Physico-Chimica Sinica, ;2021, 37(10): 191205. doi: 10.3866/PKU.WHXB201912053 shu

Photocrosslinking-Immobilized Polymer Vesicles for Lowering Temperature Triggered Drug Release

Yuyao Liao ^{1, 2} ,
Zhen Fan ^{2, 3,,} ,
Jianzhong Du ^{1, 2, 4,,}

1.
Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
2.
Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
3.
Institute for Advanced Study, Tongji University, Shanghai 200092, China
4.
Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, Tongji University, Shanghai 201804, China

Corresponding author: Zhen Fan, fanzhen2018@tongji.edu.cn Jianzhong Du, jzdu@tongji.edu.cn
Received Date: 23 December 2019
Revised Date: 13 February 2020
Accepted Date: 18 February 2020
Available Online: 2 March 2020
Fund Project: the National Natural Science Foundation of China 21674081the National Natural Science Foundation of China 21925505the National Natural Science Foundation of China 51803152the Natural Science Foundation of Shanghai, China 19ZR1478800

The stability of nanocarriers in physiological environments is of importance for biomedical applications. Among the existing crosslinking approaches for enhancing the structural integrity and stability, photocrosslinking has been considered to be an ideal crosslinking chemistry, as it is non-toxic and cost-effective, and does not require an additional crosslinker or generate by-products. Meanwhile, most current temperature-responsive nanocarriers are designed and synthesized for drug release by increasing temperature. However, heating may induce cell damage during triggered drug release. Therefore, lowering temperature-triggered nanocarriers need to be developed for drug delivery and safe drug release during therapeutic hypothermia. In this study, we prepared an amphiphilic block copolymer, poly(ethylene oxide)-block-poly[N-isopropyl acrylamide-stat-7-(2-methacryloyloxyethoxy)-4-methylcoumarin]-block-poly(acrylic acid) [PEO₄₃-b-P(NIPAM₇₁-stat-CMA₈)-b-PAA₁₃], by reversible addition fragmentation chain transfer (RAFT) polymerization. Successful synthesis of the polymer was verified by proton nuclear magnetic resonance (¹H NMR) and size exclusion chromatography (SEC). The copolymers self-assembled into vesicles in aqueous solution, with the P(NIPAM-stat-CMA) block forming an inhomogeneous membrane and the PEO chains and PAA chains forming mixed coronas. The cavity of this vesicle could be utilized to load hydrophilic drugs. The CMA groups could undergo photocrosslinking and enhance the stability of vesicles in biological applications, and the PNIPAM moiety endowed the vesicle with temperature-responsive properties. Upon decreasing the temperature, the vesicles swelled and released the loaded drugs. The size distribution and morphology of the vesicles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) experiments. After staining with phosphotungstic acid, the hollow morphology of the vesicles with a phase-separated inhomogeneous membrane was observed by TEM and SEM. The DLS results showed that the hydrodynamic diameter of the vesicles was 208 nm and the polydispersity was 0.075. The size of the vesicles observed by TEM was between 180 and 200 nm, which was in accordance with that measured by DLS. To verify the drug loading capacity and controlled release ability of the vesicle, a water-soluble antibiotic was encapsulated in the vesicles. The experimental results showed that the drug loading content was 10.4% relative to the vesicles and the drug loading efficiency was approximately 32.7%. For vesicles containing the same amount of antibiotics, the release rate at 25 ℃ was 35% higher than that at 37 ℃ after 12 h in aqueous solution. Overall, this photocrosslinked vesicle with temperature-responsive properties facilitates lowering temperature-triggered drug release during therapeutic hypothermia.
- Polymer vesicle,
- Temperature-sensitive,
- Photocrosslinking,
- Controlled drug release,
- Reversible addition fragmentation chain transfer (RAFT) polymerization
1. [1]
  Ganta, S.; Devalapally, H.; Shahiwala, A.; Amiji, M. J. Controlled Release 2008, 126, 187. doi: 10.1016/j.jconrel.2007.12.017 doi: 10.1016/j.jconrel.2007.12.017
2. [2]
  Mura, S.; Nicolas, J.; Couvreur, P. Nat. Mater. 2013, 12, 991. doi: 10.1038/nmat3776 doi: 10.1038/nmat3776
3. [3]
  Nicolas, J.; Mura, S.; Brambilla, D.; Mackiewicz, N.; Couvreur, P. Chem. Soc. Rev. 2013, 42, 1147. doi: 10.1039/c2cs35265f doi: 10.1039/c2cs35265f
4. [4]
  Zhang, L.; Xia, J.; Zhao, Q.; Liu, L.; Zhang, Z. Small 2010, 6, 537. doi: 10.1002/smll.200901680 doi: 10.1002/smll.200901680
5. [5]
  Chen, J. C.; Li, J. Z.; Liu, J. H.; Xu, L. Q. Chin. Chem. Lett. 2015, 26, 1319. doi: 10.1016/j.cclet.2015.05.050 doi: 10.1016/j.cclet.2015.05.050
6. [6]
  Sun, H.; Wang, F. Y. K.; Du, J. Z. Sci. Sin.: Chim. 2019, 49, 877. doi: 10.1039/c8sc03995j doi: 10.1039/c8sc03995j
7. [7]
  Wang, Y.; Liu, Y.; Xu, S.; Liu, H. Acta Phys. -Chim. Sin. 2019, 35, 876. doi: 10.3866/PKU.WHXB201901019
8. [8]
  Yang, B.; Du, J. Z. Chin. J. Polym. Sci. 2020, 38, 349. doi: 10.1007/s10118-020-2345-6 doi: 10.1007/s10118-020-2345-6
9. [9]
  Chen, L. S.; Hong, Y. X.; He, S. S.; Fan, Z.; Du, J. Z. Acta Phys. -Chim. Sin. 2020, 36, 1910059. doi: 10.3866/pku.whxb201910059
10. [10]
  Xiao, J. G.; Hu, Y.; Du, J. Z. Sci. China Chem. 2018, 61, 569. doi: 10.1007/s11426-017-9209-3 doi: 10.1007/s11426-017-9209-3
11. [11]
  Deng, Z.; Qian, Y.; Yu, Y.; Liu, G.; Hu, J.; Zhang, G.; Liu, S. J. Am. Chem. Soc. 2016, 138, 10452. doi: 10.1021/jacs.6b04115 doi: 10.1021/jacs.6b04115
12. [12]
  Ge, Z.; Liu, S. Chem. Soc. Rev. 2013, 42, 7289. doi: 10.1039/c3cs60048c doi: 10.1039/c3cs60048c
13. [13]
  Jin, Q.; Liu, X.; Liu, G.; Ji, J. Polymer 2010, 51, 1311. doi: 10.1016/j.polymer.2010.01.026 doi: 10.1016/j.polymer.2010.01.026
14. [14]
  Li, Y.; Xiao, K.; Zhu, W.; Deng, W.; Lam, K. S. Adv. Drug Delivery Rev. 2014, 66, 58. doi: 10.1016/j.addr.2013.09.008 doi: 10.1016/j.addr.2013.09.008
15. [15]
  Wang, F. Y. K.; Gao, J. Y.; Xiao, J. G.; Du, J. Z. Nano Lett. 2018, 18, 5562. doi: 10.1021/acs.nanolett.8b01985 doi: 10.1021/acs.nanolett.8b01985
16. [16]
  Jiang, X. Z.; Luo, S. Z.; Armes, S. P.; Shi, W. F.; Liu, S. Y. Macromolecules 2006, 39, 5987. doi: 10.1021/ma061386m doi: 10.1021/ma061386m
17. [17]
  Yang, Y. M.; Velmurugan, B.; Liu, X. G.; Xing, B. G. Small 2013, 9, 2937. doi: 10.1002/smll.201201765 doi: 10.1002/smll.201201765
18. [18]
  Wang, Q.; Cheng, M.; Jiang, J. L.; Wang, L. Y. Chin. Chem. Lett. 2017, 28, 793. doi: 10.1016/j.cclet.2017.02.008 doi: 10.1016/j.cclet.2017.02.008
19. [19]
  Liu, N.; Yi, C. L.; Sun, J. H.; Wang, J. Q.; Liu, X. Y. Acta Phys. -Chim. Sin. 2013, 29, 327. doi: 10.3866/PKU.WHXb201212032
20. [20]
  Zhao, Y. Q.; Fei, F.; Yi, C. L.; Jiang, J. Q.; Luo, J.; Liu, X. Y. Acta Phys. -Chim. Sin. 2010, 26, 3230. doi: 10.3866/PKU.WHXB20101217
21. [21]
  Li, B. J.; Wu, Y. Q.; Wang, Y.; Zhang, M. S.; Chen, H. M.; Li, J.; Liu, R. H.; Ding, Y.; Hu, A. G. ACS Appl. Mater. Interfaces 2019, 11, 8896. doi: 10.1021/acsami.8b22516 doi: 10.1021/acsami.8b22516
22. [22]
  Zhang, Y. X.; He, J.; Dai, X. C.; Yu, L. L.; Tan, J. B.; Zhang, L. Polym. Chem. 2019, 10, 3902. doi: 10.1039/c9py00534j doi: 10.1039/c9py00534j
23. [23]
  Batrakova, E. V.; Kabanov, A. V. J. Controlled Release 2008, 130, 98. doi: 10.1016/j.jconrel.2008.04.013 doi: 10.1016/j.jconrel.2008.04.013
24. [24]
  Danhier, F.; Feron, O.; Preat, V. J. Controlled Release 2010, 148, 135. doi: 10.1016/j.jconrel.2010.08.027 doi: 10.1016/j.jconrel.2010.08.027
25. [25]
  Jiang, X.; Ge, Z.; Xu, J.; Liu, H.; Liu, S. Biomacromolecules 2007, 8, 3184. doi: 10.1021/bm700743h doi: 10.1021/bm700743h
26. [26]
  Nishiyama, N.; Kataoka, K. Pharmacol. Ther. 2006, 112, 630. doi: 10.1016/j.pharmthera.2006.05.006 doi: 10.1016/j.pharmthera.2006.05.006
27. [27]
  Yang, W. T.; Guo, W. S.; Le, W. J.; Lv, G. X.; Zhang, F. H.; Shi, L.; Wang, X. L.; Wang, J.; Wang, S.; Chang, J.; et al. ACS Nano 2016, 10, 10245. doi: 10.1021/acsnano.6b05760 doi: 10.1021/acsnano.6b05760
28. [28]
  Chen, X. R.; Ding, X. B.; Zheng, Z. H.; Peng, Y. X. New J. Chem. 2006, 30, 577. doi: 10.1039/b516053g doi: 10.1039/b516053g
29. [29]
  Leal, M. P.; Torti, A.; Riedinger, A.; La Fleur, R.; Petti, D.; Cingolani, R.; Bertacco, R.; Pellegrino, T. ACS Nano 2012, 6, 10535. doi: 10.1021/nn3028425 doi: 10.1021/nn3028425
30. [30]
  Li, Y. T.; Lokitz, B. S.; Armes, S. P.; McCormick, C. L. Macromolecules 2006, 39, 2726. doi: 10.1021/ma0604035 doi: 10.1021/ma0604035
31. [31]
  Jiang, X. Z.; Liu, S. Y.; Narain, R. Langmuir 2009, 25, 13344. doi: 10.1021/la9034276 doi: 10.1021/la9034276
32. [32]
  Qu, T. H.; Wang, A. R.; Yuan, J. F.; Shi, J. H.; Gao, Q. Y. Colloids Surf., B 2009, 72, 94. doi: 10.1016/j.colsurfb.2009.03.020 doi: 10.1016/j.colsurfb.2009.03.020
33. [33]
  Sun, J. X.; Wang, Y. L.; Dou, S. H. Chin. Chem. Lett. 2012, 23, 97. doi: 10.1016/j.cclet.2011.09.023 doi: 10.1016/j.cclet.2011.09.023
34. [34]
  Huang, H. Q.; Qi, X. L.; Chen, Y. H.; Wu, Z. H. Saudi Pharm. J. 2019, 27, 990. doi: 10.1016/j.jsps.2019.08.001 doi: 10.1016/j.jsps.2019.08.001
35. [35]
  Kashcooli, M.; Salimpour, M. R.; Shirani, E. J. Therm. Biol. 2017, 64, 7. doi: 10.1016/j.jtherbio.2016.12.007 doi: 10.1016/j.jtherbio.2016.12.007
36. [36]
  Hijnen, N.; Kneepkens, E.; de Smet, M.; Langereis, S.; Heijman, E.; Grull, H. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, E4802. doi: 10.1073/pnas.1700790114 doi: 10.1073/pnas.1700790114
37. [37]
  Hildebrandt, B.; Wust, P.; Ahlers, O.; Dieing, A.; Sreenivasa, G.; Kerner, T.; Felix, R.; Riess, H. Crit. Rev. Oncol. Hemat. 2002, 43, 33. doi: 10.1016/s1040-8428(01)00179-2 doi: 10.1016/s1040-8428(01)00179-2
38. [38]
  Breslin, M.; Lam, P.; Murrell, G. A. C. BMJ Open Sport Exerc. Med. 2015, 1, e000037. doi: 10.1136/bmjsem-2015-000037 doi: 10.1136/bmjsem-2015-000037
39. [39]
  Utsunomiya, M.; Nitta, K.; Sawagichi, H.; Yoshikawa, A.; Karasuno, H.; Morozumi, K.; Allison, G. T.; Fujiwara, T.; Abe, K. J. Phys. Ther. Sci. 2010, 22, 43. doi: 10.1589/jpts.22.43 doi: 10.1589/jpts.22.43
40. [40]
  Holzer, M.; Cerchiari, E.; Martens, P.; Roine, R.; Sterz, F.; Eisenburger, P.; Havel, C.; Kofler, J.; Oschatz, E.; Rohrbach, K.; et al. N. Engl. J. Med. 2002, 346, 549. doi: 10.1056/NEJMoa012689 doi: 10.1056/NEJMoa012689
41. [41]
  Nolan, J. P.; Morley, P. T.; Hoek, T. L. V.; Hickey, R. W.; Kloeck, W. G. J.; Billi, J.; Bottiger, B. W.; Morley, P. T.; Nolan, J. P.; Okada, K.; et al. Circulation 2003, 108, 118. doi: 10.1161/01.cir.0000079019.02601.90 doi: 10.1161/01.cir.0000079019.02601.90
42. [42]
  Zhu, Y.; Liu, L.; Du, J. Macromolecules 2013, 46, 194. doi: 10.1021/ma302176a doi: 10.1021/ma302176a
43. [43]
  Lu, F.; Luo, Y.; Li, B.; Zhao, Q.; Schork, F. J. Macromolecules 2010, 43, 568. doi: 10.1021/ma902058b doi: 10.1021/ma902058b
44. [44]
  Chen, J.; Liu, Q. M.; Xiao, J. G.; Du, J. Z. Biomacromolecules 2015, 16, 1695. doi: 10.1021/acs.biomac.5b00551 doi: 10.1021/acs.biomac.5b00551
45. [45]
  Zhu, Y. Q.; Wang, F. Y. K.; Zhang, C.; Du, J. Z. ACS Nano 2014, 8, 6644. doi: 10.1021/nn502386j doi: 10.1021/nn502386j
46. [46]
  Xiao, Y. F.; Sung, H.; Du, J. Z. J. Am. Chem. Soc. 2017, 139, 7640. doi: 10.1021/jacs.7b03219 doi: 10.1021/jacs.7b03219
47. [47]
  Yuan, K.; Zhou, X.; Du, J. Z. Acta Phys. -Chim. Sin. 2017, 33, 656. doi: 10.3866/pku.whxb201701162
1. [1]
  Baoqi Wu , Rongzhi Tang , Zhi-Wei Li , Feng Lin , Zongyu Sun , Huanyu Xia , Lin Jiang , Yu Tan . Selective encapsulation of azo compounds by tetracationic cyclophane in water and photo-controlled reversible release. Chinese Chemical Letters, 2025, 36(9): 110896-. doi: 10.1016/j.cclet.2025.110896
2. [2]
  Haoyu Luo , Jinsong Chen , Mengfei Luo , Hui Ma , Shengyan Pu . Heterogeneous Fenton catalytic degradation of nitrobenzene by controlled-release nano calcium peroxide. Chinese Chemical Letters, 2025, 36(6): 110367-. doi: 10.1016/j.cclet.2024.110367
3. [3]
  Chunlei Dai , Liying Wang , Xinru You , Yi Zhao , Zhong Cao , Jun Wu . Coffee-derived self-anti-inflammatory polymer as drug nanocarrier for enhanced rheumatoid arthritis treatment. Chinese Chemical Letters, 2025, 36(3): 109869-. doi: 10.1016/j.cclet.2024.109869
4. [4]
  Mengyuan Li , Xitong Ren , Yanmei Gao , Mengyao Mu , Shiping Zhu , Shufang Tian , Minghua Lu . Constructing bifunctional magnetic porous poly(divinylbenzene) polymer for high-efficient removal and sensitive detection of bisphenols. Chinese Chemical Letters, 2024, 35(12): 109699-. doi: 10.1016/j.cclet.2024.109699
5. [5]
  Jing REN , Ruikui YAN , Xiaoli CHEN , Huali CUI , Hua YANG , Jijiang WANG . Synthesis and fluorescence sensing of a highly sensitive and multi-response cadmium coordination polymer. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 574-586. doi: 10.11862/CJIC.20240287
6. [6]
  Xiang Li , Beibei Zhang , Zhixiang Wang , Xiangyu Chen . Organocatalyzed iodine-mediated reversible-deactivation radical polymerization via photoinduced charge transfer complex catalysis. Chinese Chemical Letters, 2025, 36(6): 110383-. doi: 10.1016/j.cclet.2024.110383
7. [7]
  Chenkai Yang , Xiaoling Pan , Weiguang Zhao , Zhiwen Qiu , Lei He , Cong Wu , Ang Li , Zhengnan Huang , Yilin Yan , Shengzhou Li , Zhuofan Nan , Xiangqian Cao , Bing Shen , Wei Li . Intratumoral photo-controlled antigens burst release for synergistic immunotherapy by bio-membrane and organic membrane coated dual-functional nanoparticles. Chinese Chemical Letters, 2025, 36(9): 110740-. doi: 10.1016/j.cclet.2024.110740
8. [8]
  Zeyin Chen , Jiaju Shi , Yusheng Zhou , Peng Zhang , Guodong Liang . Polymer microparticles with ultralong room-temperature phosphorescence for visual and quantitative detection of oxygen through phosphorescence image and lifetime analysis. Chinese Chemical Letters, 2025, 36(5): 110629-. doi: 10.1016/j.cclet.2024.110629
9. [9]
  Wen Su , Siying Liu , Qingfu Zhang , Zhongyan Zhou , Na Wang , Lei Yue . Temperature-controlled electrospray ionization tandem mass spectrometry study on protein/small molecule interaction. Chinese Chemical Letters, 2025, 36(5): 110237-. doi: 10.1016/j.cclet.2024.110237
10. [10]
  Wanting CHEN , Chufei MIAO , Yan LIU , Bobi ZHENG , Xiaoyu ZHENG , Han XU , Jumei TIAN . Syntheses, characterization, and luminescence properties of Yb(Ⅲ)-based one-dimensional chain coordination polymer. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1672-1680. doi: 10.11862/CJIC.20250013
11. [11]
  Ming Huang , Xiuju Cai , Yan Liu , Zhuofeng Ke . Base-controlled NHC-Ru-catalyzed transfer hydrogenation and α-methylation/transfer hydrogenation of ketones using methanol. Chinese Chemical Letters, 2024, 35(7): 109323-. doi: 10.1016/j.cclet.2023.109323
12. [12]
  Bing Niu , Honggao Huang , Liwei Luo , Li Zhang , Jianbo Tan . Coating colloidal particles with a well-defined polymer layer by surface-initiated photoinduced polymerization-induced self-assembly and the subsequent seeded polymerization. Chinese Chemical Letters, 2025, 36(2): 110431-. doi: 10.1016/j.cclet.2024.110431
13. [13]
  Feng Shi , Guiling Li , Haibing Zhu , Ling Li , Ming Chen , Juan Li , Huifang Shen , Hao Zeng , Lingfeng Min , Zhanjun Yang . Nanozyme-triggered polymerization amplification strategy for constructing highly sensitive surface plasmon resonance immunosensing. Chinese Chemical Letters, 2025, 36(6): 110333-. doi: 10.1016/j.cclet.2024.110333
14. [14]
  Yan Wang , Si-Meng Zhai , Peng Luo , Xi-Yan Dong , Jia-Yin Wang , Zhen Han , Shuang-Quan Zang . Vapor- and temperature-triggered reversible optical switching for multi-response Cu₈ cluster supercrystals. Chinese Chemical Letters, 2024, 35(11): 109493-. doi: 10.1016/j.cclet.2024.109493
15. [15]
  Keke Li , Haiquan Wang , Zhen-Kun He , Yan-Yan Song , Zhida Gao , Chenxi Zhao . Engineering Cl vacancies in lead-free halide double perovskites decorated on TiO₂ nanotubes for highly sensitive NO₂ sensing at room temperature. Chinese Chemical Letters, 2025, 36(8): 110610-. doi: 10.1016/j.cclet.2024.110610
16. [16]
  Xiaoman Dang , Zhiying Wu , Tangxin Xiao , Zhouyu Wang , Leyong Wang . Highly robust supramolecular polymer networks crosslinked by metallacycles. Chinese Chemical Letters, 2024, 35(12): 110208-. doi: 10.1016/j.cclet.2024.110208
17. [17]
  Yaohua Li , Qi Cao , Xuanhua Li . Tailoring the configuration of polymer passivators in perovskite solar cells. Chinese Journal of Structural Chemistry, 2025, 44(2): 100413-100413. doi: 10.1016/j.cjsc.2024.100413
18. [18]
  Yuwei Liu , Yihui Zhu , Weijian Duan , Yizhuo Yang , Haorui Tuo , Chunhua Feng . Electrocatalytic nitrate reduction on Fe, Fe₃O₄, and Fe@Fe₃O₄ cathodes: Elucidating structure-sensitive mechanisms of direct electron versus hydrogen atom transfer. Chinese Chemical Letters, 2025, 36(6): 110347-. doi: 10.1016/j.cclet.2024.110347
19. [19]
  Zhuan Chen , Bo Yang , Jun Li , Kun Du , Jiangchen Fu , Xiao Wu , Jiazhen Cao , Mingyang Xing . Environmentally safe storage and sustained release of hydrogen peroxide utilizing commercial hydrogel. Chinese Chemical Letters, 2025, 36(6): 110320-. doi: 10.1016/j.cclet.2024.110320
20. [20]
  Tiankai Sun , Hui Min , Zongsu Han , Liang Wang , Peng Cheng , Wei Shi . Rapid detection of nanoplastic particles by a luminescent Tb-based coordination polymer. Chinese Chemical Letters, 2024, 35(5): 108718-. doi: 10.1016/j.cclet.2023.108718

Get Citation

PDF

XML

Metrics

PDF Downloads(6)
Abstract views(428)
HTML views(35)

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