Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Graphical Abstract
Abstract
Keywords
Electronic Supplementary Material
References
Show full outline
Hide outline
Research Article

Manganese-doped mesoporous polydopamine nanoagent for T1-T2 magnetic resonance imaging and tumor therapy

Xiuqi Hou1,§, Xi Yang1,§, Yanwen Xu3,§, Jiayin Lin1, Fang Zhang2, Xiaohui Duan2, Sitong Liu1, Jie Liu1, Jun Shen2, Xintao Shuai4(), Zhong Cao1()
School of Biomedical Engineering, Sun Yat-sen University, Guangzhou 510006, China
Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Translational Medicine Institute, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518035, China
Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China

§ Xiuqi Hou, Xi Yang, and Yanwen Xu contributed equally to this work.

Show Author Information

Graphical Abstract

View original image Download original image
A novel theranostic nanoagent was constructed for T1-T2 magnetic resonance imaging (MRI) and combination therapy of cancer. The nanoagent released R848 to repolarize the tumor associated macrophages into the tumor-suppressing M1 phenotype, and produced NO to perform synergistic anti-tumor effects. Furthermore, the T1-T2 bimodal MRI ability makes the nanoagent a promising candidate for MRI-guided cancer therapy.

Abstract

Theranostic nanodrugs combining magnetic resonance imaging (MRI) and cancer therapy have attracted extensive interest in cancer diagnosis and treatment. Herein, a manganese (Mn)-doped mesoporous polydopamine (Mn-MPDA) nanodrug incorporating the nitric oxide (NO) prodrug BNN6 and immune agonist R848 was developed. The nanodrug responded to the H+ and glutathione being enriched in tumor microenvironment to release R848 and Mn2+. The abundant Mn2+ produced through a Fenton-like reaction enabled a highly sensitive T1-T2 dual-mode MRI for monitoring the tumor accumulation process of the nanodrug, based on which an MRI-guided laser irradiation was achieved to trigger the NO gas therapy. Meanwhile, R848 induced the re-polarization of tumor-promoting M2-like macrophage to a tumoricidal M1 phenotype. Consequently, a potent synergistic antitumor effect was realized in mice bearing subcutaneous 4T1 breast cancer, which manifested the great promise of this multifunctional nanoplatform in cancer treatment.

Keywords

mesoporous polydopaminemagnetic resonance imagingT1-T2 dual-modeNO gas therapyimmunotherapy

Electronic Supplementary Material

Download File(s)
12274_2022_4877_MOESM1_ESM.pdf (1.6 MB)

References

[1]

Zhou, Z. J.; Bai, R. L.; Munasinghe, J.; Shen, Z. Y.; Nie, L. M.; Chen, X. Y. T1-T2 dual-modal magnetic resonance imaging: From molecular basis to contrast agents. ACS Nano 2017, 11, 5227–5232.

Crossref Google Scholar
[2]

Glunde, K.; Artemov, D.; Penet, M. F.; Jacobs, M. A.; Bhujwalla, Z. M. Magnetic resonance spectroscopy in metabolic and molecular imaging and diagnosis of cancer. Chem. Rev. 2010, 110, 3043–3059.

Crossref Google Scholar
[3]

Zhou, Z. J.; Yang, L. J.; Gao, J. H.; Chen, X. Y. Structure–relaxivity relationships of magnetic nanoparticles for magnetic resonance imaging. Adv. Mater. 2019, 31, e1804567.

Crossref Google Scholar
[4]

Yang, M. D.; Ho, C. H.; Ruta, S.; Chantrell, R.; Krycka, K.; Hovorka, O.; Chen, F. R.; Lai, P. S.; Lai, C. H. Magnetic interaction of multifunctional core–shell nanoparticles for highly effective theranostics. Adv. Mater. 2018, 30, e1802444.

Crossref Google Scholar
[5]

Pablico-Lansigan, M. H.; Situ, S. F.; Samia, A. C. Magnetic particle imaging: Advancements and perspectives for real-time in vivo monitoring and image-guided therapy. Nanoscale 2013, 5, 4040–4055.

Crossref Google Scholar
[6]

Zhou, Z. J.; Huang, D. T.; Bao, J. F.; Chen, Q. L.; Liu, G.; Chen, Z.; Chen, X. Y.; Gao, J. H. A synergistically enhanced T1-T2 dual-modal contrast agent. Adv. Mater. 2012, 24, 6223–6228.

Crossref Google Scholar
[7]

Bhooshan, N.; Giger, M.; Lan, L.; Li, H.; Marquez, A.; Shimauchi, A.; Newstead, G. M. Combined use of T2-weighted MRI and T1-weighted dynamic contrast-enhanced MRI in the automated analysis of breast lesions. Magn. Reson. Med. 2011, 66, 555–564.

Crossref Google Scholar
[8]

Gong, H.; Dong, Z. L.; Liu, Y. M.; Yin, S. N.; Cheng, L.; Xi, W. Y.; Xiang, J.; Liu, K.; Li, Y. G.; Liu, Z. Engineering of multifunctional nano-micelles for combined photothermal and photodynamic therapy under the guidance of multimodal imaging. Adv. Funct. Mater. 2014, 24, 6492–6502.

Crossref Google Scholar
[9]

Krogsgaard, M.; Behrens, M. A.; Pedersen, J. S.; Birkedal, H. Self-healing mussel-inspired multi-pH-responsive hydrogels. Biomacromolecules 2013, 14, 297–301.

Crossref Google Scholar
[10]

Guo, L. Q.; Liu, Q.; Li, G. L.; Shi, J. B.; Liu, J. Y.; Wang, T.; Jiang, G. B. A mussel-inspired polydopamine coating as a versatile platform for the in situ synthesis of graphene-based nanocomposites. Nanoscale 2012, 4, 5864–5867.

Crossref Google Scholar
[11]

Wu, D.; Duan, X. H.; Guan, Q. Q.; Liu, J.; Yang, X.; Zhang, F.; Huang, P.; Shen, J.; Shuai, X. T.; Cao, Z. Mesoporous polydopamine carrying manganese carbonyl responds to tumor microenvironment for multimodal imaging-guided cancer therapy. Adv. Funct. Mater. 2019, 29, 1900095.

Crossref Google Scholar
[12]

Chen, L. C.; Zhou, S. F.; Su, L. C.; Song, J. B. Gas-mediated cancer bioimaging and therapy. ACS Nano 2019, 13, 10887–10917.

Crossref Google Scholar
[13]

Xu, W. M.; Liu, L. Z.; Loizidou, M.; Ahmed, M.; Charles, I. G. The role of nitric oxide in cancer. Cell Res. 2002, 12, 311–320.

Crossref Google Scholar
[14]

Khan, F. H.; Dervan, E.; Bhattacharyya, D. D.; McAuliffe, J. D.; Miranda, K. M.; Glynn, S. A. The role of nitric oxide in cancer: Master regulator or not? Int. J. Mol. Sci. 2020, 21, 9393.

Crossref Google Scholar
[15]

Xu, J. S.; Zeng, F.; Wu, H.; Hu, C. P.; Yu, C. M.; Wu, S. Z. Preparation of a mitochondria-targeted and no-releasing nanoplatform and its enhanced pro-apoptotic effect on cancer cells. Small 2014, 10, 3750–3760.

Crossref Google Scholar
[16]

Lee, J.; Hlaing, S. P.; Hasan, N.; Kwak, D.; Kim, H.; Cao, J. F.; Yoon, I. S.; Yun, H.; Jung, Y.; Yoo, J. W. Tumor-penetrable nitric oxide-releasing nanoparticles potentiate local antimelanoma therapy. ACS Appl. Mater. Interfaces 2021, 13, 30383–30396.

Crossref Google Scholar
[17]

Szabo, C. Gasotransmitters in cancer: From pathophysiology to experimental therapy. Nat. Rev. Drug Discov. 2016, 15, 185–203.

Crossref Google Scholar
[18]

Dou, Y.; Zhao, F. S.; Li, X.; Guo, Y. Y. Monitoring nitric oxide-induced hypoxic tumor radiosensitization by radiation-activated nanoagents under BOLD/DWI imaging. ACS Biomater. Sci. Eng. 2021, 7, 5242–5254.

Crossref Google Scholar
[19]

Paul, S.; Pan, S.; Mukherjee, A.; De, P. Nitric oxide releasing delivery platforms: Design, detection, biomedical applications, and future possibilities. Mol. Pharm. 2021, 18, 3181–3205.

Crossref Google Scholar
[20]

Li, S. H.; Liu, R.; Jiang, X. X.; Qiu, Y.; Song, X. R.; Huang, G. M.; Fu, N. Y.; Lin, L. S.; Song, J. B.; Chen, X. Y. et al. Near-infrared light-triggered sulfur dioxide gas therapy of cancer. ACS Nano 2019, 13, 2103–2113.

Crossref Google Scholar
[21]

He, Q. J. Precision gas therapy using intelligent nanomedicine. Biomater. Sci. 2017, 5, 2226–2230.

Crossref Google Scholar
[22]

Fan, J.; He, N. Y.; He, Q. J.; Liu, Y.; Ma, Y.; Fu, X.; Liu, Y. J.; Huang, P.; Chen, X. Y. A novel self-assembled sandwich nanomedicine for NIR-responsive release of NO. Nanoscale 2015, 7, 20055–20062.

Crossref Google Scholar
[23]

Deng, Y. Y.; Jia, F.; Chen, S. Y.; Shen, Z. D.; Jin, Q.; Fu, G. S.; Ji, J. Nitric oxide as an all-rounder for enhanced photodynamic therapy: Hypoxia relief, glutathione depletion and reactive nitrogen species generation. Biomaterials 2018, 187, 55–65.

Crossref Google Scholar
[24]

Binnewies, M.; Roberts, E. W.; Kersten, K.; Chan, V.; Fearon, D. F.; Merad, M.; Coussens, L. M.; Gabrilovich, D. I.; Ostrand-Rosenberg, S.; Hedrick, C. C. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 2018, 24, 541–550.

Crossref Google Scholar
[25]

Xiao, H.; Guo, Y.; Li, B.; Li, X. X.; Wang, Y.; Han, S. S.; Cheng, D.; Shuai, X. T. M2-like tumor-associated macrophage-targeted codelivery of STAT6 inhibitor and IKKβ siRNA induces M2-to-M1 repolarization for cancer immunotherapy with low immune side effects. ACS Cent. Sci. 2020, 6, 1208–1222.

Crossref Google Scholar
[26]

Tang, X. Q.; Mo, C. F.; Wang, Y. S.; Wei, D. D.; Xiao, H. Y. Anti-tumour strategies aiming to target tumour-associated macrophages. Immunology 2013, 138, 93–104.

Crossref Google Scholar
[27]

DeNardo, D. G.; Ruffell, B. Macrophages as regulators of tumour immunity and immunotherapy. Nat. Rev. Immunol. 2019, 19, 369–382.

Crossref Google Scholar
[28]

Nadeem, A.; Siddiqui, N.; Al-Harbi, N. O.; Al-Harbi, M. M.; Ahmad, S. F. TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma. Int. J. Biochem. Cell Biol. 2016, 73, 53–62.

Crossref Google Scholar
[29]

Hemmi, H.; Kaisho, T.; Takeuchi, O.; Sato, S.; Sanjo, H.; Hoshino, K.; Horiuchi, T.; Tomizawa, H.; Takeda, K.; Akira, S. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 2002, 3, 196–200.

Crossref Google Scholar
[30]

Lee, M.; Park, C. S.; Lee, Y. R.; Im, S. A.; Song, S.; Lee, C. K. Resiquimod, a TLR7/8 agonist, promotes differentiation of myeloid-derived suppressor cells into macrophages and dendritic cells. Arch. Pharm. Res. 2014, 37, 1234–1240.

Crossref Google Scholar
[31]

Loré, K.; Betts, M. R.; Brenchley, J. M.; Kuruppu, J.; Khojasteh, S.; Perfetto, S.; Roederer, M.; Seder, R. A.; Koup, R. A. Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J. Immunol. 2003, 171, 4320–4328.

Crossref Google Scholar
[32]

Wang, Y. K.; Liu, Y.; Wu, H. X.; Zhang, J. P.; Tian, Q. W.; Yang, S. P. Functionalized holmium-doped hollow silica nanospheres for combined sonodynamic and hypoxia-activated therapy. Adv. Funct. Mater. 2019, 29, 1805764.

Crossref Google Scholar
[33]

Hao, Y. N.; Zheng, A. Q.; Guo, T. T.; Shu, Y.; Wang, J. H.; Johnson, O.; Chen, W. Glutathione triggered degradation of polydopamine to facilitate controlled drug release for synergic combinational cancer treatment. J. Mater. Chem. B 2019, 7, 6742–6750.

Crossref Google Scholar
[34]

Ma, Z. W.; Xiang, X. Q.; Li, S. Y.; Xie, P.; Gong, Q.; Goh, B. C.; Wang, L. Z. Targeting hypoxia-inducible factor-1, for cancer treatment: Recent advances in developing small-molecule inhibitors from natural compounds. Semin. Cancer Biol. 2022, 80, 379–390.

Crossref Google Scholar
[35]

Sung, Y. C.; Jin, P. R.; Chu, L. A.; Hsu, F. F.; Wang, M. R.; Chang, C. C.; Chiou, S. J.; Qiu, J. T.; Gao, D. Y.; Lin, C. C. et al. Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies. Nat. Nanotechnol. 2019, 14, 1160–1169.

Crossref Google Scholar
[36]

Ridnour, L. A.; Isenberg, J. S.; Espey, M. G.; Thomas, D. D.; Roberts, D. D.; Wink, D. A. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc. Natl. Acad. Sci. USA 2005, 102, 13147–13152.

Crossref Google Scholar
Nano Research
Volume 16 Issue 2,
February 2023
Pages 2991-3003
DOI: 10.1007/s12274-022-4877-4
Cite this article:
Hou X, Yang X, Xu Y, et al. Manganese-doped mesoporous polydopamine nanoagent for T1-T2 magnetic resonance imaging and tumor therapy. Nano Research, 2023, 16(2): 2991-3003. https://doi.org/10.1007/s12274-022-4877-4
Topics:
Magnetic resonance imaging
Metrics & Citations  
Article History
Copyright
Return