English
新闻公告
More
化学进展 2017, Vol. 29 Issue (10): 1195-1205 DOI: 10.7536/PC170411 前一篇   后一篇

• 综述 •

肿瘤免疫治疗中的生物医用载体

陈璐扬, 赵瑾, 龙丽霞, 侯信, 原续波*   

  1. 天津大学材料科学与工程学院 天津市材料复合与功能化重点实验室 天津 300072
  • 收稿日期:2017-04-13 修回日期:2017-08-22 出版日期:2017-10-15 发布日期:2017-08-29
  • 通讯作者: 原续波,e-mail:xbyuan@tju.edu.cn E-mail:xbyuan@tju.edu.cn
  • 基金资助:
    国家自然科学基金项目(No.51473119)资助

Biological Carrier for Tumor Immunotherapy

Xubo Yuan, Jin Zhao, Lixia Long, Xin Hou, Xubo Yuan*   

  1. School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China
  • Received:2017-04-13 Revised:2017-08-22 Online:2017-10-15 Published:2017-08-29
  • Supported by:
    The work was supported by the National Natural Science Foundation of China (No. 51473119).
免疫治疗是目前一种新型的肿瘤治疗手段,通过引入并增强功能性的抗原特异性免疫反应,来实现对肿瘤细胞长期持续的免疫记忆、预防和杀伤。与传统化疗相比,肿瘤免疫治疗毒副作用较轻,可获得较好的临床治疗效果。免疫治疗从最初的抗原疫苗类,发展到目前以嵌合抗原受体T淋巴细胞(CAR-T)为代表的过继免疫细胞治疗,治疗效果不断提高。但与此同时,多种免疫治疗手段尚存在一定问题:治疗性蛋白、核酸等自身靶向性差,在体内向靶点呈递过程遇到降解、物理屏障等,及自身免疫原性引起的潜在毒性,均有待进一步完善。将多样化生物医用材料应用于免疫治疗中,即应用载体运输蛋白、核酸有助于解决以上问题。目前,载体在肿瘤免疫治疗中包含以下几个功能:(1)减少治疗性药物如蛋白质和核酸的降解;(2)提高靶向性;(3)协助跨物理屏障;(4)减少全身副作用;(5)实现持续性释放。本文沿肿瘤免疫治疗发展进程,综述多样化的新型生物医用材料载体在肿瘤免疫治疗中的特殊作用和最新进展,并指出其存在的不足和可能面对的挑战。
Aimed at acquiring long-term immune memory, prevention and tumor killing, immunotherapy is a new method for tumor therapy by introducing and enhancing the antigen specific immune response. Compared with the traditional chemotherapy, tumor immunotherapy has less side effects and shows better clinical response. From the original antigen vaccine to the current development of adoptive cell therapy such as chimeric antigen receptor T lymphocytes (CAR-T), the treatment effect has been improved. However, some problems still exist in immunotherapies:the poor targeting property of therapeutic protein and nucleic acid, the difficulty in crossing the physical barrier, the inclination to be degraded, as well as the potential toxicity caused by immunogenicity, all of which require further improvement for better immunotherapeutic strategy. As effective carries for loading proteins and nucleic acids, a variety of biomedical materials are used to solve the above problems. At present, the biological carriers contain several functions in immunotherapy:(1) reduce the degradation of therapeutic substances such as protein and nucleic acid; (2) enhance targeting of conditioned drugs; (3) assist to cross the physical barrier; (4) reduce systemic side effects; (5) achieve persistent release. In this article, the latest development of new biomedical material carriers is introduced, and the existing problems and the possible challenges are also put forward.
Contents
1 Introduction
2 Tumor antigen vaccine
3 Cytokine immunotherapy
4 Gene immunotherapy
4.1 Polymer carrier
4.2 Metal and inorganic nano-carrier
5 Monoclonal antibody immunotherapy
5.1 Polymer nanoparticle carrier
5.2 Injectable hydrogel carrier
6 Adoptive immunotherapy
6.1 Superparamagnetic iron oxide nanoparticle carrier
6.2 Gel carrier
7 Conclusion

中图分类号: 

()
[1] Jemal A, Bray F, Center M M, Ferlay J, Ward E, Forman D. CA Cancer J. Clin., 2011, 61:69.
[2] Tang H D, Qiao J, Fu Y X. Cancer Lett., 2016, 370:85.
[3] Restifo N P, Smyth M J, Snyder A. Nat. Rev. Cancer, 2016, 16:121.
[4] Steinman R M, Banchereau J. Nature, 2007, 449:419.
[5] Palucka K, Banchereau J. Curr. Opin. Immunol., 2013, 25:396.
[6] Schreiber T H, Raez L, Rosenblatt J D, Podack E R. Semin. Immunol., 2010, 22:105.
[7] Rosenthal J A, Chen L X, Baker J L, Putnam D, DeLisa M P. Curr. Opin. Biotechnol., 2014, 28:51.
[8] Moon J J, Suh H, Bershteyn A, Stephan M T, Liu H P, Huang B, Sohail M, Luo S, Um S H, Khant H, Goodwin J T, Ramos J, Chiu W, Irvine D J. Nat. Mater., 2011, 10:243.
[9] Liu Q, Jia J L, Yang T, Fan Q Z, Wang L Y, Ma G H. Small, 2016, 12:1744.
[10] Rosalia R A, Cruz L J, van Duikeren S, Tromp A T, Silva A L, Jiskoot W, de Gruijl T, Lowik C, Oostendorp J, van der Burg S H, Ossendorp F. Biomaterials, 2015, 40:88.
[11] Shao K, Singha S, Clemente-Casares X, Tsai S, Yang Y, Santamaria P. ACS Nano, 2015, 9:16.
[12] Hamdy S, Haddadi A, Hung R W, Lavasanifar A. Adv. Drug Deliv. Rev., 2011, 63:943.
[13] Hassan H A F M, Smyth L, Wang J T W, Costa P M, Ratnasothy K, Diebold S S, Lombardi G, Al-Jamal K T. Biomaterials, 2016, 104:310.
[14] Tacken P J, Zeelenberg I S, Cruz L J, van Hout-Kuijer M A, van de Glind G, Fokkink R G, Lambeck A J A, Figdor C G. Blood, 2011, 118:6836.
[15] 张茜(Zhang Q), 朱艳红(Zhu Y H), 徐辉碧(Xu H B), 杨祥良(Yang X L). 化学进展(Progress in Chemistry), 2015, 27(2/3):275.
[16] Dranoff G. Nat. Rev. Cancer, 2004, 4:11.
[17] Parkhurst M R, Riley J P, Dudley M E, Rosenberg S A. Clin. Cancer Res., 2011, 17:6287.
[18] Wu J J, Tang C, Yin C H. Acta Biomater., 2017, 47:81.
[19] Deo V K, Kato T, Park E Y. J. Pharm. Sci., 2016, 105:1614.
[20] Klibanov A L, Maruyama K, Torchilin V P, Huang L. FEBS Lett., 1990, 268:235.
[21] Park J, Wrzesinski S H, Stern E, Look M, Criscione J, Ragheb R, Jay S M, Demento S L, Agawu A, Licona Limon P, Ferrandino A F, Gonzalez D, Habermann A, Flavell R A, Fahmy T M. Nat. Mater., 2012, 11:895.
[22] Mundargi R C, Babu V R, Rangaswamy V, Patel P, Aminabhavi T M. J. Controlled Release, 2008, 125:193.
[23] 廖荣强(Liao R Q), 刘满朔(Liu M S), 廖霞俐(Liao X L), 杨波(Yang B). 化学进展(Progress in Chemistry), 2015, 27(1):79.
[24] Cruz L J, Tacken P J, Fokkink R, Figdor C G. Biomaterials, 2011, 32:6791.
[25] Seo S H, Han H D, Noh K H, Kim T W, Son S W. Clin. Exp. Metastasis, 2009, 26:179.
[26] Li S D, Huang L. J. Controlled Release, 2007, 123:181.
[27] Park T G, Jeong J H, Kim S W. Adv. Drug Deliv. Rev., 2006, 58:467.
[28] Christensen L V, Chang C W, Won J K, Sung W K, Zhong Z Y, Lin C, Engbersen J F J, Feijen J. Bioconjugate Chem., 2006, 17:1233.
[29] Hatakeyama H, Murata M, Sato Y, Takahashi M, Minakawa N, Matsuda A, Harashima H. J. Controlled Release, 2014, 173:43.
[30] Wang H Y, Jiang Y F, Peng H G, Chen Y Z, Zhu P Z, Huang Y Z. Adv. Drug Deliv. Rev., 2015, 81:142.
[31] Lungwitz U, Breunig M, Blunk T, Göpferich A. Eur. J. Pharm. Biopharm., 2005, 60:247.
[32] Peng C H, Cherng J Y, Chiou G Y, Chen Y C, Chien C H, Kao C L, Chang Y L, Chien Y, Chen L K, Liu J H, Chen S J, Chiou S H. Biomaterials, 2011, 32:9077.
[33] Lai S K, Suk J S, Pace A, Wang Y Y, Yang M, Mert O, Chen J, Kim J, Hanes J. Biomaterials., 2011, 32:6285.
[34] Neu M, Fischer D, Kissel T. J. Gene Med., 2005, 7:992.
[35] Kim A J, Boylan N J, Suk J S, Hwangbo M, Yu T, Schuster B S, Cebotaru L, Lesniak W G, Oh J S, Adstamongkonkul P, Choi A Y, Kannan R M, Hanes J. Angew. Chem. Int. Ed., 2013, 52:3985.
[36] Chiou G Y, Cherng J Y, Hsu H S, Wang M L, Tsai C M, Lu K H, Chien Y, Hung S C, Chen Y W, Wong C I, Tseng L M, Huang P I, Yu C C, Hsu W H, Chiou S H. J. Controlled Release, 2012, 159:240.
[37] Xu C F, Zhang H B, Sun C Y, Liu Y, Shen S, Yang X Z, Zhu Y H, Wang J. Biomaterials, 2016, 88:48.
[38] Kumar M N V R, Muzzarelli R A A, Muzzarelli C, Sashiwa H, Domb A J. Chem. Rev., 2004, 104:6017.
[39] Katas H, Alpar H O. J. Controlled Release, 2006, 115:216.
[40] Lee D W, Yun K S, Ban H S, Choe W, Lee S K, Lee K Y. J. Controlled Release, 2009, 139:146.
[41] Lee J, Yun K S, Choi C S, Shin S H, Ban H S, Rhim T, Lee S K, Lee K Y. Bioconjugate Chem., 2012, 23:1174.
[42] Liu C Y, Wen J, Meng Y B, Zhang K L, Zhu J L, Ren Y, Qian X M, Yuan X B, Lu Y F, Kang C. Adv. Mater., 2015, 27:292.
[43] Qian X M, Long L X, Shi Z D, Liu C Y, Qiu M Z, Sheng J, Pu P Y, Yuan X B, Ren Y, Kang C S. Biomaterials, 2014, 35:2322.
[44] Vallhov H, Kupferschmidt N, Gabrielsson S, Paulie S, Strømme M, Garcia-Bennett A E, Scheynius A. Small, 2012, 8:2116.
[45] Liu T L, Liu H Y, Fu C H, Li L L, Chen D, Zhang Y Q, Tang F Q. J. Colloid Interface Sci., 2013, 400:168.
[46] Almeida J P M, Figueroa E R, Drezek R A. Nanomedicine, 2014, 10:503.
[47] Wang Y R, Wang Y, Kang N, Liu Y L, Shan W J, Bi S L, Ren L, Zhuang G H. Nanoscale Res. Lett., 2016, 11:1.
[48] Lee I H, Kwon H K, An S, Kim D, Kim S, Yu M K, Lee J H, Lee T S, Im S H, Jon S. Angew. Chem. Int. Ed. Engl., 2012, 51:8800.
[49] Krieg A M. Nat. Rev. Drug Discov., 2006, 5:471.
[50] Fabbro C, Ali-Boucetta H, Ros T D, Kostarelos K, Bianco A, Prato M. Chem. Commun., 2012, 48:3911.
[51] Han Z J, Ostrikov K, Tan C M, Tay B K, Peel S A F. Nanotechnology, 2011, 22:295712.
[52] Costa P M, Bourgognon M, Wang J T W, Al-Jamal K T. J. Controlled Release, 2016, 241:200.
[53] de Faria P C, dos Santos L I, Coelho J P, Ribeiro H B, Pimenta M A, Ladeira L O, Gomes D A, Furtado C A, Gazzinelli R T. Nano Lett., 2014, 14:5458.
[54] Marchesan S, Prato M. Chem. Commun., 2015, 51:4347.
[55] Liu Z, Tabakman S, Welsher K, Dai H J. Nano Res., 2009, 2:85.
[56] He C L, Tang Z H, Tian H Y, Chen X S. Adv. Drug Deliv. Rev., 2016, 98:64.
[57] Scott A M, Wolchok J D, Old L J. Nat. Rev. Cancer, 2012, 12:278.
[58] LoRusso P M, Weiss D, Guardino E, Girish S, Sliwkowski M X. Clin. Cancer Res., 2011, 17:6437.
[59] Hu C M J, Aryal S, Zhang L F. Ther. Deliv., 2010, 1:323.
[60] Jiang T Y, Mo R, Bellotti A, Zhou J P, Gu Z. Adv. Funct. Mater., 2014, 24:2295.
[61] Lee A L Z, Ng V W L, Gao S J, Hedrick J L, Yang Y Y. Adv. Funct. Mater., 2014, 24:1538.
[62] Aoki M, Okudaira K, Haga M, Nishigaki R, Hayashi M. Drug Metab. Dispos., 2010, 38:1183.
[63] Lee A L Z, Wang Y, Cheng H Y, Pervaiz S, Yang Y Y. Biomaterials, 2009, 30:919.
[64] Sun B F, Feng S S. Nanomedicine, 2009, 4:431.
[65] Shi M, Ho K, Keating A, Shoichet M S. Adv. Funct. Mater., 2009, 19:1689.
[66] Mi Y, Zhao J, Feng S S. J. Controlled Release, 2013, 169:185.
[67] Kedar U, Phutane P, Shidhaye S, Kadam V. Nanomedicine, 2010, 6:714
[68] Perche F, Patel N R, Torchilin V P. J. Controlled Release, 2012, 164:95.
[69] Li W, Zhao H, Qian W Z, Li H F, Zhang L, Ye Z W, Zhang G, Xia M, Li J F, Gao J, Li B H, Kou G, Dai J X, Wang H, Guo Y J. Biomaterials, 2012, 33:5362.
[70] Akagi T, Baba M, Akashi M. Advances in Polymer Science. NY:Springer-Verlag Berlin Heidelberg, 2011. 247.
[71] Li Y K, Fang M, Zhang J, Wang J, Song Y, Shi J, Li W, Wu G, Ren J H, Wang Z, Zou W P, Wang L. Oncoimmunology, 2016, 5:e1074374.
[72] Rosenberg S A, Restifo N P. Science, 2015, 348:62.
[73] Turtle C J, Hanafi L A, Berger C, Gooley T A, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto T M, Robinson E, Steevens N, Chaney C, Soma L, Chen X Y, Yeung C, Wood B, Li D, Cao J H, Heimfeld S, Jensen M, Riddell S R, Maloney D G. J. Clin. Oncol., 2015, 33:3006.
[74] Ager A, Watson H A, Wehenkel S C, Mohammed R N. Biochem. Soc. Trans., 2016, 44:377.
[75] Kakarla S, Gottschalk S. Cancer J., 2014, 20:151.
[76] Adusumilli P S, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, Jones D R, Sadelain M. Sci. Transl. Med., 2014, 6:261ra151.
[77] Gilham D E, Debets R, Pule M, Hawkins R E, Abken H. Trends Mol. Med., 2012, 18:377.
[78] Melero I, Rouzaut A, Motz G T, Coukos G. Cancer Discov., 2014, 4:522.
[79] Melero I, Hervas-Stubbs S, Glennie M, Pardoll D M, Chen L P. Nat. Rev. Cancer, 2007, 7:95.
[80] Jin H L, Qian Y, Dai Y F, Qiao S, Huang C, Lu L S, Luo Q M, Chen J, Zhang Z H. Theranostics, 2016, 6:2000.
[81] Stephan S B, Taber A M, Jileaeva I, Pegues E P, Sentman C L, Stephan M T. Nat. Biotechnol., 2015, 33:97.
[82] Matsuno R, Ishihara K. Nano Today, 2011, 6:61.
[1] 陈一明, 李慧颖, 倪鹏, 方燕, 刘海清, 翁云翔. 含儿茶酚基团的湿态组织粘附水凝胶[J]. 化学进展, 2023, 35(4): 560-576.
[2] 李良春, 郑仁林, 黄毅, 孙荣琴. 多组分自组装小分子水凝胶中的自分类组装[J]. 化学进展, 2023, 35(2): 274-286.
[3] 陈浩, 徐旭, 焦超男, 杨浩, 王静, 彭银仙. 多功能核壳结构纳米反应器的构筑及其催化性能[J]. 化学进展, 2022, 34(9): 1911-1934.
[4] 顾顺心, 姜琴, 施鹏飞. 发光铱(Ⅲ)配合物抗肿瘤活性研究及应用[J]. 化学进展, 2022, 34(9): 1957-1971.
[5] 宝利军, 危俊吾, 钱杨杨, 王雨佳, 宋文杰, 毕韵梅. 酶响应性线形-树枝状嵌段共聚物的合成、性能及应用[J]. 化学进展, 2022, 34(8): 1723-1733.
[6] 冯海弟, 赵璐, 白云峰, 冯锋. 纳米金属有机框架在肿瘤靶向治疗中的应用[J]. 化学进展, 2022, 34(8): 1863-1878.
[7] 陈晓峰, 王开元, 梁芳铭, 姜睿祺, 孙进. 外泌体递药系统及其在肿瘤治疗中的应用[J]. 化学进展, 2022, 34(4): 773-786.
[8] 刘洋洋, 赵子刚, 孙浩, 孟祥辉, 邵光杰, 王振波. 后处理技术提升燃料电池催化剂稳定性[J]. 化学进展, 2022, 34(4): 973-982.
[9] 李红, 史晓丹, 李洁龄. 肽自组装水凝胶的制备及在生物医学中的应用[J]. 化学进展, 2022, 34(3): 568-579.
[10] 宫悦, 程一竹, 胡银春. 高分子导电水凝胶的制备及在柔性可穿戴电子设备中的应用[J]. 化学进展, 2022, 34(3): 616-629.
[11] 杨林颜, 郭宇鹏, 李正甲, 岑洁, 姚楠, 李小年. 钴基费托合成催化剂的表界面性质调控[J]. 化学进展, 2022, 34(10): 2254-2266.
[12] 王嘉莉, 朱凌, 王琛, 雷圣宾, 杨延莲. 循环肿瘤细胞及细胞外囊泡的纳米检测技术[J]. 化学进展, 2022, 34(1): 178-197.
[13] 宋路杰, 吴友平, 邓建平. 手性药物的对映体选择性释放[J]. 化学进展, 2021, 33(9): 1550-1559.
[14] 荆晓东, 孙莹, 于冰, 申有青, 胡浩, 丛海林. 肿瘤微环境响应药物递送系统的设计[J]. 化学进展, 2021, 33(6): 926-941.
[15] 李立清, 吴盼旺, 马杰. 双网络凝胶吸附剂的构建及其去除水中污染物的应用[J]. 化学进展, 2021, 33(6): 1010-1025.
阅读次数
全文


摘要

肿瘤免疫治疗中的生物医用载体