Bionanoparticles with In Situ Nitric Oxide Release for Precise Modulation of ER-TRPV1 Ion Channels in Multimodal Killing of Glioblastoma
Chaoqun Li
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Cixi Institute of Biomedical Engineering, Ningbo, 315201 P. R. China
Search for more papers by this authorJinlei Peng
MOE Key Laboratory of High-Performance Polymer Materials and Technology, Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023 P. R. China
Search for more papers by this authorBing Wang
Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Cixi Institute of Biomedical Engineering, Ningbo, 315201 P. R. China
Search for more papers by this authorDong Gao
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Search for more papers by this authorXiaoning Liu
School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130 P. R. China
Search for more papers by this authorGuodong Cheng
School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130 P. R. China
Search for more papers by this authorBoying Li
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Search for more papers by this authorRan Zhang
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Search for more papers by this authorXintao Shuai
Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 P. R. China
Search for more papers by this authorCorresponding Author
Fude Feng
MOE Key Laboratory of High-Performance Polymer Materials and Technology, Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Chengfen Xing
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorChaoqun Li
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Cixi Institute of Biomedical Engineering, Ningbo, 315201 P. R. China
Search for more papers by this authorJinlei Peng
MOE Key Laboratory of High-Performance Polymer Materials and Technology, Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023 P. R. China
Search for more papers by this authorBing Wang
Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Cixi Institute of Biomedical Engineering, Ningbo, 315201 P. R. China
Search for more papers by this authorDong Gao
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Search for more papers by this authorXiaoning Liu
School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130 P. R. China
Search for more papers by this authorGuodong Cheng
School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130 P. R. China
Search for more papers by this authorBoying Li
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Search for more papers by this authorRan Zhang
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
Search for more papers by this authorXintao Shuai
Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 P. R. China
Search for more papers by this authorCorresponding Author
Fude Feng
MOE Key Laboratory of High-Performance Polymer Materials and Technology, Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Chengfen Xing
Innovation and Research Institute of Hebei University of Technology in Shijiazhuang, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Xiping Road, Tianjin, 300130 P. R. China
School of Materials Science and Engineering, Hebei University of Technology, Tianjin, 300130 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
Glioblastoma (GBM) with highly immunosuppressive tumor microenvironment is a significant factor contributing to its treatment resistance and low survival rate. The activation of the transient receptor potential vanilloid 1 (TRPV1) ion channel, which is overexpressed on the endoplasmic reticulum (ER) of GBM cells, governs the control of multi-organelle stress pathway branches to inhibit GBM expansion. Precise modulation of ER-TRPV1 is considered an effective strategy for inhibition of GBM. As an effective intracellular and extracellular second messenger, nitric oxide (•NO) activates the TRPV1 ion channel through nitrosylation of cysteine residues. However, the short lifespan and limited effective range of •NO makes it challenging to achieve precise regulation of ER-TRPV1. Herein, a biomimetic upconversion nanoassembly (M-UCN-T) is constructed, which encapsulates an organic •NO donor and is coated with homologous tumor-targeting cell membrane and ER-targeting peptide. In response to near-infrared light and glutathione, M-UCN-T releases •NO in situ to activate the ER-TRPV1 ion channels. This study developed a •NO-targeted release nanoplatform with stepwise targeting functions, which allow for the precise modulation of ER-TPRV1 in GBM through in situ release of •NO. This approach induces multi-organelle stress signaling pathways, ultimately resulting in multi-modal killing of tumor cells.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
| Filename | Description |
|---|---|
| smll202408649-sup-0001-SuppMat.docx2.9 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1a) E. De Fazio, M. Pittarello, A. Gans, B. Ghosh, H. Slika, P. Alimonti, B. Tyler, Int. J. Mol. Sci. 2024, 25, 2563; b) A. P. Patel, I. Tirosh, J. J. Trombetta, A. K. Shalek, S. M. Gillespie, H. Wakimoto, D. P. Cahill, B. V. Nahed, W. T. Curry, R. L. Martuza, D. N. Louis, R. O. Rozenblatt, M. L. Suvà, A. Regev, B. E. Bernstein, Science. 2014, 344, 1396. c) A. Gieryng, D. Pszczolkowska, K. A. Walentynowicz, W. D. Rajan, B. Kaminska, Lab. Invest. 2017, 97, 498.
- 2a) J. F. Zhao, S. K. Shyue, T. S. Lee, Int. J. Biol. Sci. 2016, 12, 18; b) T. Yoshida, R. Inoue, T. Morii, N. Takahashi, S. Yamamoto, Y. Hara, M. Tominaga, S. Shimizu, Y. Sato, Y. Mori, Nat. Chem. Biol. 2006, 2, 596; c) J. Park, K. Jin, A. Sahasrabudhe, P. H. Chiang, J. H. Maalouf, F. Koehler, D. Rosenfeld, S. Rao, T. Tanaka, T. Khudiyev, Z. J. Schiffer, Y. Fink, O. Yizhar, K. Manthiram, P. Anikeeva, Nat. Nanotechnol. 2020, 15, 690; d) S. S. Sen, D. J. Lee, Â. Crespo, J. J. Hu, C. Walker, X. Ma, Y. Zhang, S. Chowdhury, K. F. Meza-Sosa, M. Lewandrowski, H. Zhang, M. Rowe, A. McClelland, H. Wu, C. Junqueira, J. Lieberman, Nature. 2023, 618, E17.
- 3K. Stock, J. Kumar, M. Synowitz, S. Petrosino, R. Imperatore, E. S. Smith, P. Wend, B. Purfürst, U. A. Nuber, U. Gurok, V. Matyash, J. H. Wälzlein, S. R. Chirasani, G. Dittmar, B. F. Cravatt, S. Momma, G. R. Lewin, A. Ligresti, P. L. De, L. Cristino, V. Di Marzo, H. Kettenmann, R. Glass, Nat. Med. 2012, 18, 1232.
- 4M. Mulier, J. Vriens, T. Voets, Cell Calcium. 2017, 66, 19.
- 5a) C. Li, D. Gao, Y. Gao, R. Zhang, X. Qu, S. Li, C. Xing, Adv. Healthcare Mater. 2023, 12, 2301954; b) C. Li, S. Shi, D. Gao, B. Li, G. Song, Y. Chen, H. An, C. Xing, ACS Appl. Mater. & Interfaces. 2022, 14, 31715; c) B. Li, S. Ren, D. Gao, N. Li, M. Wu, H. Yuan, M. Zhou, C. Xing, Adv. Healthcare Mater. 2022, 11, 2102506; d) B. Li, N. Li, L. Chen, S. Ren, D. Gao, H. Geng, J. Fu, M. Zhou, C. Xing, ACS Appl. Mater. & Interfaces. 2022, 14, 48416; e) B. Li, Y. Wang, D. Gao, S. Ren, L. Li, N. Li, H. An, T. Zhu, Y. Yang, H. Zhang, C. Xing, Adv. Funct. Mater. 2021, 31, 2010757; f) X. Wu, Y. Jiang, N. J. Rommelfanger, F. Yang, Q. Zhou, R. Yin, J. Liu, S. Cai, W. Ren, A. Shin, Nat. Biomed. Eng. 2022, 6, 754; g) J. Yuan, H. Liu, H. Zhang, T. Wang, Q. Zheng, Z. Li, Adv. Mater. 2022, 34, 2108435; h) X. Zhen, C. Xie, Y. Jiang, X. Ai, B. Xing, K. Pu, Nano Lett. 2018, 18, 1498; i) Q. Huang, W. Zhu, X. Gao, X. Liu, Z. Zhang, B. Xing, Adv. Drug Delivery Rev. 2023, 195, 114763; j) Y. Lyu, C. Xie, S. A. Chechetka, E. Miyako, K. Pu, J. Am. Chem. Soc. 2016, 138, 9049; k) N. Li, C. Li, B. Li, C. Li, Q. Zhao, Z. Huang, Y. Shu, X. Qu, B. Wang, S. Li, Nano Lett. 2023, 23, 10608.
- 6a) K. Stock, J. Kumar, M. Synowitz, S. Petrosino, R. Imperatore, E. St J Smith, P. Wend, B. Purfürst, U. A. Nuber, U. Gurok, V. Matyash, J. Wälzlein, S. R. Chirasani, G. Dittmar, B. F. Cravatt, S. Momma, G. R. Lewin, A. Ligresti, L. D. Petrocellis, L. Cristino, V. D. Marzo, H. Kettenmann, R. Glass, Nat. Med. 2012, 18, 1232; b) A. Rp, B. Am, C. Ma, D. Bf, E. Mr, A. Gr, C. Aca, F. Lbc, C. Sp, D. Sk, Redox Biol. 2020, 37, 101705; c) L. Zhou, F. Lv, L. Liu, S. Wang, CCS Chem. 2019, 1, 97; d) X. Wang, Y. Qiu, M. Wang, C. Zhang, T. Zhang, H. Zhou, W. Zhao, W. Zhao, G. Xia, R. Shao, Int. J. Nanomed. 2020, 15, 9447; e) J. Sun, X. Zhang, X. Wang, J. Peng, G. Song, Y. Di, F. Feng, S. Wang, Angew. Chem., Int. Ed. 2022, 134, 202213765; f) W. Chen, M. Chen, Q. Zang, L. Wang, F. Tang, Y. Han, C. Yang, D. Liu, Y. Liu, Chem. Commun. 2015, 51, 9193; g) X. Chu, X. Jiang, Y. Liu, S. Zhai, W. Bu, Adv. Funct. Mater. 2021, 31, 2008507.
- 7a) G. J. Chen, Y. J. Cai, B. Li, M. Z. Lin, X. B. Wang, Z. Y. Wang, X. T. Shuai, Sci. China Chem. 2022, 65, 1383; b) E. Nagababu, Free. Radic. Bio. Med. 2016, 101, 296.
- 8a) D. Zheng, R. L. Birke, J. Am. Chem. Soc. 2002, 124, 9066; b) J. J. Hu, L. Yuan, Y. Zhang, J. Kuang, W. Song, X. Lou, F. Xia, J. Yoon, Angew. Chem., Int. Ed. 2024, 63, 202317578.
- 9a) J. Park, K. Jin, A. Sahasrabudhe, P.-H. Chiang, J. H. Maalouf, F. Koehler, D. Rosenfeld, S. Rao, T. Tanaka, T. Khudiyev, Nat. Nanotechnol. 2020, 15, 690; b) R. Guo, Y. Tian, Y. Wang, W. Yang, Adv. Funct. Mater. 2017, 27, 1606398.
- 10a) X. Zhang, J. Du, Z. Guo, J. Yu, Q. Gao, W. Yin, S. Zhu, Z. Gu, Y. Zhao, Adv. Sci. 2018, 6, 1801122;
10.1002/advs.201801122 Google Scholarb) Y. J. Fu, X. Zhao, L. Y. Wang, K. Li, N. Jiang, S. T. Zhang, R. K. Wang, Y. F. Zhao, W. A. Yang, Adv. Mater. 2024, 36, 2309972; c) Z. C. Xu, Q. Z. Luo, Y. Q. He, Y. C. He, X. W. Zhang, J. Wang, N. Song, D. W. Gao, Adv. Funct. Mater. 2024, 34, 2314536; d) H. Shi, C. F. Xiong, L. J. Zhang, H. C. Cao, R. Wang, P. Pan, H. Y. Guo, T. Liu, Adv. Healthcare Mater. 2023, 12, 2300012; e) M. L. Kang, H. S. Kim, J. You, Y. S. Choi, B. J. Kwon, C. H. Park, W. Baek, M. S. Kim, Y. J. Lee, G. I. Im, J. K. Yoon, J. B. Lee, H. J. Sung, Sci. Adv. 2020, 6, eaay5413; f) Z. Deng, J. Zhang, J. Zhou, W. Shen, Y. Zuo, J. Wang, S. Yang, J. Liu, Y. Chen, C. C. Chen, G. Jia, P. Alam, J. W. Y. Lam, B. Z. Tang, Adv. Mater. 2024, 36, 2311384; g) J. Shao, H. Xie, H. Huang, Z. Li, Z. Sun, Y. Xu, Q. Xiao, X. F. Yu, Y. Zhao, H. Zhang, Nat. Commun. 2016, 7, 12967.
- 11J. Sun, X. Cai, C. Wang, K. Du, W. Chen, F. Feng, S. Wang, J. Am. Chem. Soc. 2021, 143, 868.
- 12Q. Gao, X. Zhang, W. Yin, D. Ma, C. Xie, L. Zheng, X. Dong, L. Mei, J. Yu, C. Wang, Small. 2018, 14, 1802290.
- 13a) Z. Shen, S. Zheng, S. Xiao, R. Shen, S. Liu, J. Hu, Angew. Chem., Int. Ed. 2021, 133, 20615;
10.1002/ange.202107155 Google Scholarb) X. Bao, S. Zheng, L. Zhang, A. Shen, G. Zhang, S. Liu, J. Hu, Angew. Chem., Int. Ed. 2022, 134, 202207250;10.1002/ange.202207250 Google Scholarc) Z. Wang, H. Geng, C. Nie, C. Xing, Chin. J. Chem. 2022, 40, 759.
- 14a) A. Spang, Curr. Opin. Cell Biol. 2018, 53, 92; b) L. Galluzzi, T. Yamazaki, G. Kroemer, Nat. Rev. Mol. Cell Biol. 2018, 19, 731.
- 15X. Wang, J. Qian, Z. Yang, Y. Song, W. Pan, Y. Ye, X. Qin, X. Yan, X. Huang, X. Wang, Adv. Mater. 2024, 36, 2310964.
- 16W. Li, J. Yang, L. Luo, M. Jiang, B. Qin, H. Yin, C. Zhu, X. Yuan, J. Zhang, Z. Luo, Nat. Commun. 2019, 10, 3349.
- 17H. Kojima, N. Nakatsubo, K. Kikuchi, S. Kawahara, Y. Kirino, H. Nagoshi, Y. Hirata, T. Nagano, Anal. Chem. 1998, 70, 2446.
- 18Y. Liu, Y. Lu, B. Ning, X. Su, B. Yang, H. Dong, B. Yin, Z. Pang, S. Shen, ACS Nano. 2022, 16, 4102.
- 19a) T. Inoue, H. Maekawa, R. Inagi, Kidney Int. 2019, 95, 1318; b) W. M. Henne, Dev. Cell. 2021, 56, 878.
- 20a) M. Song, J. R. Cubillos-Ruiz, Trends. Immunol. 2019, 40, 128; b) S. Zheng, X. Wang, D. Zhao, H. Liu, Y. Hu, Trends. Cell. Biol. 2023, 33, 312.
- 21S. S. Santara, D. J. Lee, N. Crespo, J. J. Hu, C. Walker, X. Ma, Y. Zhang, S. Chowdhury, K. F. Meza-Sosa, M. Lewandrowski, Nature. 2023, 618, E17.
- 22E. Repges, M. Al Zaidi, F. Jansen, S. Zimmer, V. Tiyerlili, A. Aksoy, Eur. Heart. J. 2022, 43, ehac544.
10.1093/eurheartj/ehac544.2938 Google Scholar
- 23M. Melis, K. L. Simpson, S. J. Dovedi, A. Welman, M. MacFarlane, C. Dive, J. Honeychurch, T. M. Illidge, Cell Death & Differ. 2013, 20, 765.
- 24J. Luo, Y. Xia, J. Luo, J. Li, C. Zhang, H. Zhang, T. Ma, L. Yang, L. Kong, Cancer Lett. 2017, 410, 112.
- 25O. Kepp, L. Menger, E. Vacchelli, C. Locher, S. Adjemian, T. Yamazaki, I. Martins, A. Q Sukkurwala, M. Michaud, L. Senovilla, L. Galluzzi, G. Kroemer, L. Zitvogel, Cytokine. Growth. Factor Rev. 2013, 24, 311.
- 26M. J. Barrera, S. Aguilera, I. Castro, J. Cortés, M. J. González, J. Autoimmun. 2016, 75, 68.
