ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Interleukin-2 Functionalized Nanocapsules for T Cell-Based Immunotherapy

View Author Information
Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz D-55099, Germany
Max Planck Institute for Polymer Research, Mainz D-55128, Germany
Cite this: ACS Nano 2016, 10, 10, 9216–9226
Publication Date (Web):October 10, 2016
https://doi.org/10.1021/acsnano.5b07973
Copyright © 2016 American Chemical Society

    Article Views

    2820

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    A major demand on immunotherapy is the direct interference with specific immune cells in vivo. In contrast to antibody-engineered nanoparticles to control dendritic cells function, targeting of T cells for biomedical applications still remains an obstacle as they disclose reduced endocytic activities. Here, by coupling the cytokine interleukin-2 (IL-2) to the surface of hydroxyethyl starch nanocapsules, we demonstrated a direct and specifc T cell targeting in vitro and in vivo by IL-2 receptor-mediated internalization. For this purpose, defined amounts of azide-functionalized IL-2 were linked to alkyne-functionalized hydroxyethyl starch nanocapsules via copper-free click reactions. In combination with validated quantification of the surface-linked IL-2 with anthracen azide, this method allowed for engineering IL-2-functionalized nanocapsules for an efficient targeting of human and murine T cell populations with various IL-2 receptor affinities. This nanocapsule-mediated technique is a promising strategy for T cell-based immunotherapies and may be translated to other cytokine-related targeting systems.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.5b07973.

    • Synthesis and functionalization of HES nanocapsules; Synthesis of 9-(azidomethyl)anthracene (anth-N3); In Vivo application of nanocapsules. Figure S1a: IL-2 functionalization of HES nanocapsules in a multistep process: miniemulsion. Figure S1b: IL-2 functionalization of HES nanocapsules in a multistep process. Figure S1c: IL-2 functionalization of HES nanocapsules in a multistep process: MALDI-TOF. Figure S1d: IL-2 functionalization of HES nanocapsules in a multistep process: HPLC. Figure S2: Biological activity of IL-2 on IL-2-dependent murine CTLL-2 cells. Figure S3: Nanocapsule uptake by human CD4+CD25high T cells. Figure S4: Human CD4+CD25high T cell proliferation induced by HES-D-IL-2. Figure S5: Nanocapsule-induced cytotoxicity. Figure S6: Basiliximab did not affect the uptake of control HES-D nanocapsules in human CD4+CD25+ T cells. Figure S7: HES-D-IL-2, HES-D-IL-2/2, and HES-D-IL-2/10-induced CTLL-2 proliferation. Figure S8: Phenotype and uptake of human naïve CD4+CD25, activated effector CD4+CD25+, and regulatory CD4+ CD25high T cell populations. Figure S9: Uptake of HES-D-IL-2, HES-D-IL-2/2, and HES-D-IL-2/10 nanocapsules by human naïve CD4+CD25, activated CD4+CD25+, and regulatory CD4+CD25high T cells. Figure S10: In vivo uptake of HES-D-IL-2 nanocapsules (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 42 publications.

    1. V. S. S. Abhinav Ayyadevara, Armin Ahmadi, Kyung-Ho Roh. Targeted Association and Intracellular Delivery of Nanocargoes into Primary T Lymphocytes via Interleukin-2 Receptor-Mediated Endocytosis. Bioconjugate Chemistry 2021, 32 (8) , 1675-1687. https://doi.org/10.1021/acs.bioconjchem.1c00212
    2. Zhongning Liu, Xin Chen, Zhanpeng Zhang, Xiaojin Zhang, Laura Saunders, Yongsheng Zhou, Peter X. Ma. Nanofibrous Spongy Microspheres To Distinctly Release miRNA and Growth Factors To Enrich Regulatory T Cells and Rescue Periodontal Bone Loss. ACS Nano 2018, 12 (10) , 9785-9799. https://doi.org/10.1021/acsnano.7b08976
    3. Rui Ge, Cangwei Liu, Xue Zhang, Wenjing Wang, Binxi Li, Jie Liu, Yi Liu, Hongchen Sun, Daqi Zhang, Yuchuan Hou, Hao Zhang, Bai Yang. Photothermal-Activatable Fe3O4 Superparticle Nanodrug Carriers with PD-L1 Immune Checkpoint Blockade for Anti-metastatic Cancer Immunotherapy. ACS Applied Materials & Interfaces 2018, 10 (24) , 20342-20355. https://doi.org/10.1021/acsami.8b05876
    4. Bikram Keshari Agrawalla, Tao Wang, Andreas Riegger, Matthias P. Domogalla, Kerstin Steinbrink, Thilo Dörfler, Xi Chen, Felix Boldt, Markus Lamla, Jens Michaelis, Seah Ling Kuan, Tanja Weil. Chemoselective Dual Labeling of Native and Recombinant Proteins. Bioconjugate Chemistry 2018, 29 (1) , 29-34. https://doi.org/10.1021/acs.bioconjchem.7b00675
    5. Wenpei Fan, Bryant Yung, Peng Huang, and Xiaoyuan Chen . Nanotechnology for Multimodal Synergistic Cancer Therapy. Chemical Reviews 2017, 117 (22) , 13566-13638. https://doi.org/10.1021/acs.chemrev.7b00258
    6. Paula T. Hammond . Nano Tools Pave the Way to New Solutions in Infectious Disease. ACS Infectious Diseases 2017, 3 (8) , 554-558. https://doi.org/10.1021/acsinfecdis.7b00104
    7. Dominika Berdecka, Stefaan C. De Smedt, Winnok H. De Vos, Kevin Braeckmans. Non-viral delivery of RNA for therapeutic T cell engineering. Advanced Drug Delivery Reviews 2024, 208 , 115215. https://doi.org/10.1016/j.addr.2024.115215
    8. Qingqing Li, Xinyu Fan, Xiaohan Pan, Ying Yu, Lingyan Jian, Yu Zhang, Tian Yin, Haibing He, Xing Tang, Jian Jin, Jingxin Gou. S/O/W microparticles prepared with hydroxyethyl starch-based emulsifier showed reduced macrophage affinity. Colloids and Surfaces B: Biointerfaces 2022, 220 , 112917. https://doi.org/10.1016/j.colsurfb.2022.112917
    9. Safiye Akkın, Gamze Varan, Davut Aksüt, Milo Malanga, Ayşe Ercan, Murat Şen, Erem Bilensoy. A different approach to immunochemotherapy for colon Cancer: Development of nanoplexes of cyclodextrins and Interleukin-2 loaded with 5-FU. International Journal of Pharmaceutics 2022, 623 , 121940. https://doi.org/10.1016/j.ijpharm.2022.121940
    10. Xianbin Ma, Shu-Jin Li, Yuantong Liu, Tian Zhang, Peng Xue, Yuejun Kang, Zhi-Jun Sun, Zhigang Xu. Bioengineered nanogels for cancer immunotherapy. Chemical Society Reviews 2022, 51 (12) , 5136-5174. https://doi.org/10.1039/D2CS00247G
    11. Wen Nie, Jing Chen, Bilan Wang, Xiang Gao. Nonviral vector system for cancer immunogene therapy. MedComm – Biomaterials and Applications 2022, 1 (1) https://doi.org/10.1002/mba2.10
    12. Maximilian Haist, Volker Mailänder, Matthias Bros. Nanodrugs Targeting T Cells in Tumor Therapy. Frontiers in Immunology 2022, 13 https://doi.org/10.3389/fimmu.2022.912594
    13. Lili Zhou, Manshu Zou, Yilin Xu, Peng Lin, Chang Lei, Xinhua Xia. Nano Drug Delivery System for Tumor Immunotherapy: Next-Generation Therapeutics. Frontiers in Oncology 2022, 12 https://doi.org/10.3389/fonc.2022.864301
    14. Mengjie Wang, Chunxin Wang, Shuaikai Ren, Junqian Pan, Yan Wang, Yue Shen, Zhanghua Zeng, Haixin Cui, Xiang Zhao. Versatile Oral Insulin Delivery Nanosystems: From Materials to Nanostructures. International Journal of Molecular Sciences 2022, 23 (6) , 3362. https://doi.org/10.3390/ijms23063362
    15. Zhengting Jiang, Wenjie Zhang, Jie Zhang, Tian Liu, Juan Xing, Huan Zhang, Dong Tang. Nanomaterial-Based Drug Delivery Systems: A New Weapon for Cancer Immunotherapy. International Journal of Nanomedicine 2022, Volume 17 , 4677-4696. https://doi.org/10.2147/IJN.S376216
    16. Jenny Lou, Alexandra Heater, Gang Zheng. Improving the Delivery of Drugs and Nucleic Acids to T Cells Using Nanotechnology. Small Structures 2021, 2 (8) https://doi.org/10.1002/sstr.202100026
    17. Savannah E. Est-Witte, Natalie K. Livingston, Mary O. Omotoso, Jordan J. Green, Jonathan P. Schneck. Nanoparticles for generating antigen-specific T cells for immunotherapy. Seminars in Immunology 2021, 56 , 101541. https://doi.org/10.1016/j.smim.2021.101541
    18. Kwang-Soo Kim, Dong-Hwan Kim, Dong-Hyun Kim. Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles. Pharmaceutics 2021, 13 (4) , 525. https://doi.org/10.3390/pharmaceutics13040525
    19. Yuming Yang, Minjie Xu, Zhe Wang, Yanqing Yang, Jie Liu, Qinglian Hu, Lin Li, Wei Huang. Immune remodeling triggered by photothermal therapy with semiconducting polymer nanoparticles in combination with chemotherapy to inhibit metastatic cancers. Journal of Materials Chemistry B 2021, 9 (11) , 2613-2622. https://doi.org/10.1039/D0TB02903C
    20. Huimin Wang, Hang Hu, Hai Yang, Zifu Li. Hydroxyethyl starch based smart nanomedicine. RSC Advances 2021, 11 (6) , 3226-3240. https://doi.org/10.1039/D0RA09663F
    21. Vincent Mittelheisser, Mainak Banerjee, Xavier Pivot, Loïc J. Charbonnière, Jacky Goetz, Alexandre Detappe. Leveraging Immunotherapy with Nanomedicine. Advanced Therapeutics 2020, 3 (12) https://doi.org/10.1002/adtp.202000134
    22. Alam Zeb, Isra Rana, Ho-Ik Choi, Cheol-Ho Lee, Seong-Woong Baek, Chang-Wan Lim, Namrah Khan, Sadia Tabassam Arif, Najam us Sahar, Arooj Mohsin Alvi, Fawad Ali Shah, Fakhar ud Din, Ok-Nam Bae, Jeong-Sook Park, Jin-Ki Kim. Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals. Pharmaceutics 2020, 12 (12) , 1184. https://doi.org/10.3390/pharmaceutics12121184
    23. Kristin N. Bauer, Johanna Simon, Volker Mailänder, Katharina Landfester, Frederik R. Wurm. Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers. Acta Biomaterialia 2020, 116 , 318-328. https://doi.org/10.1016/j.actbio.2020.09.016
    24. Simone Hager, Frederic Julien Fittler, Ernst Wagner, Matthias Bros. Nucleic Acid-Based Approaches for Tumor Therapy. Cells 2020, 9 (9) , 2061. https://doi.org/10.3390/cells9092061
    25. Verena K. Raker, Christian Becker, Katharina Landfester, Kerstin Steinbrink. Targeted Activation of T Cells with IL-2-Coupled Nanoparticles. Cells 2020, 9 (9) , 2063. https://doi.org/10.3390/cells9092063
    26. Lu Lu, Bing Li, Chuanchuan Lin, Ke Li, Genhua Liu, Zengzilu Xia, Zhong Luo, Kaiyong Cai. Redox-responsive amphiphilic camptothecin prodrug nanoparticles for targeted liver tumor therapy. Journal of Materials Chemistry B 2020, 8 (17) , 3918-3928. https://doi.org/10.1039/D0TB00285B
    27. Kenneth K.W. To, William C.S. Cho. Drugs repurposed to potentiate immunotherapy for cancer treatment. 2020, 311-334. https://doi.org/10.1016/B978-0-12-819668-7.00012-9
    28. Yaping Ju, Hao Guo, Maria Edman, Sarah F. Hamm-Alvarez. Application of advances in endocytosis and membrane trafficking to drug delivery. Advanced Drug Delivery Reviews 2020, 157 , 118-141. https://doi.org/10.1016/j.addr.2020.07.026
    29. Raweewan Thiramanas, Shuai Jiang, Johanna Simon, Katharina Landfester, Volker Mailänder. <p>Silica Nanocapsules with Different Sizes and Physicochemical Properties as Suitable Nanocarriers for Uptake in T-Cells</p>. International Journal of Nanomedicine 2020, Volume 15 , 6069-6084. https://doi.org/10.2147/IJN.S246322
    30. Zhenfu Wen, Fengyu Liu, Qing Chen, Yongqian Xu, Hongjuan Li, Shiguo Sun. Recent development in biodegradable nanovehicle delivery system-assisted immunotherapy. Biomaterials Science 2019, 7 (11) , 4414-4443. https://doi.org/10.1039/C9BM00961B
    31. Eun Sook Lee, Jung Min Shin, Soyoung Son, Hyewon Ko, Wooram Um, Seok Ho Song, Jae Ah Lee, Jae Hyung Park. Recent Advances in Polymeric Nanomedicines for Cancer Immunotherapy. Advanced Healthcare Materials 2019, 8 (4) https://doi.org/10.1002/adhm.201801320
    32. Banu Iyisan, Katharina Landfester. Modular Approach for the Design of Smart Polymeric Nanocapsules. Macromolecular Rapid Communications 2019, 40 (1) https://doi.org/10.1002/marc.201800577
    33. Shengxian Li, Xiangru Feng, Jixue Wang, Liang He, Chunxi Wang, Jianxun Ding, Xuesi Chen. Polymer nanoparticles as adjuvants in cancer immunotherapy. Nano Research 2018, 11 (11) , 5769-5786. https://doi.org/10.1007/s12274-018-2124-7
    34. Lien Lybaert, Karim Vermaelen, Bruno G. De Geest, Lutz Nuhn. Immunoengineering through cancer vaccines – A personalized and multi-step vaccine approach towards precise cancer immunity. Journal of Controlled Release 2018, 289 , 125-145. https://doi.org/10.1016/j.jconrel.2018.09.009
    35. Loek J. Eggermont, Roel Hammink, Kerstin G. Blank, Alan E. Rowan, Jurjen Tel, Carl G. Figdor. Cytokine‐Functionalized Synthetic Dendritic Cells for T Cell Targeted Immunotherapies. Advanced Therapeutics 2018, 1 (6) https://doi.org/10.1002/adtp.201800021
    36. Manuel Tonigold, Johanna Simon, Diego Estupiñán, Maria Kokkinopoulou, Jonas Reinholz, Ulrike Kintzel, Anke Kaltbeitzel, Patricia Renz, Matthias P. Domogalla, Kerstin Steinbrink, Ingo Lieberwirth, Daniel Crespy, Katharina Landfester, Volker Mailänder. Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona. Nature Nanotechnology 2018, 13 (9) , 862-869. https://doi.org/10.1038/s41565-018-0171-6
    37. Sonja Kübelbeck, Jules Mikhael, Harald Keller, Rupert Konradi, Annette Andrieu‐Brunsen, Grit Baier. Enzyme–Polymer Conjugates to Enhance Enzyme Shelf Life in a Liquid Detergent Formulation. Macromolecular Bioscience 2018, 18 (7) https://doi.org/10.1002/mabi.201800095
    38. Hang Hu, Jiangling Wan, Xuetao Huang, Yuxiang Tang, Chen Xiao, Huibi Xu, Xiangliang Yang, Zifu Li. iRGD-decorated reduction-responsive nanoclusters for targeted drug delivery. Nanoscale 2018, 10 (22) , 10514-10527. https://doi.org/10.1039/C8NR02534G
    39. Michele Graciotti, Cristiana Berti, Harm-Anton Klok, Lana Kandalaft. The era of bioengineering: how will this affect the next generation of cancer immunotherapy?. Journal of Translational Medicine 2017, 15 (1) https://doi.org/10.1186/s12967-017-1244-2
    40. Tanja Weil, Matthias Barz. From Polymers to Functional Biomaterials. Macromolecular Bioscience 2017, 17 (10) https://doi.org/10.1002/mabi.201700307
    41. Xue-Nan Sun, Chao Li, Yuan Liu, Lin-Juan Du, Meng-Ru Zeng, Xiao-Jun Zheng, Wu-Chang Zhang, Yan Liu, Mingjiang Zhu, Deping Kong, Li Zhou, Limin Lu, Zhu-Xia Shen, Yi Yi, Lili Du, Mu Qin, Xu Liu, Zichun Hua, Shuyang Sun, Huiyong Yin, Bin Zhou, Ying Yu, Zhiyuan Zhang, Sheng-Zhong Duan. T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma. Circulation Research 2017, 120 (10) , 1584-1597. https://doi.org/10.1161/CIRCRESAHA.116.310480
    42. Lauren Milling, Yuan Zhang, Darrell J. Irvine. Delivering safer immunotherapies for cancer. Advanced Drug Delivery Reviews 2017, 114 , 79-101. https://doi.org/10.1016/j.addr.2017.05.011

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect