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  2. Upregulating Aggregation-Induced-Emission Nanoparticles with Blood-Tumor-Barrier Permeability for Precise Photothermal Eradication of Brain Tumors and Induction of Local Immune Responses

Upregulating Aggregation-Induced-Emission Nanoparticles with Blood-Tumor-Barrier Permeability for Precise Photothermal Eradication of Brain Tumors and Induction of Local Immune Responses

  • Adv Mater. 2021 Jun;33(22):e2008802. doi: 10.1002/adma.202008802.
Ming Zhang 1 Wentao Wang 1 Mohsen Mohammadniaei 1 Tao Zheng 1 Qicheng Zhang 2 Jon Ashley 1 Shunjie Liu 3 4 Yi Sun 1 Ben Zhong Tang 5
Affiliations

Affiliations

  • 1 Department of Health Technology, Technical University of Denmark, Kongens Lyngby, DK-2800, Denmark.
  • 2 Jiangsu Collaborative Innovation Center for Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023, P. R. China.
  • 3 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
  • 4 School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, P. R. China.
  • 5 Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, P. R. China.
Abstract

Compared to other tumors, glioblastoma (GBM) is extremely difficult to treat. Recently, photothermal therapy (PTT) has demonstrated advanced therapeutic efficacy; however, because of the relatively low tissue-penetration efficiency of laser LIGHT, its application in deep-seated tumors remains challenging. Herein, bradykinin (BK) aggregation-induced-emission nanoparticles (BK@AIE NPs) are synthesized; these offer selective penetration through the blood-tumor barrier (BTB) and strong absorbance in the near-infrared region (NIR). The BK ligand can prompt BTB Adenosine Receptor activation, which enhances transportation and accumulation inside tumors, as confirmed by T1 -weighted magnetic resonance and fluorescence imaging. The BK@AIE NPs exhibit high photothermal conversion efficiency under 980 nm NIR laser irradiation, facilitating the treatment of deep-seated tumors. Tumor progression can be effectively inhibited to extend the survival span of mice after spatiotemporal PTT. NIR irradiation can eradicate tumor tissues and release tumor-associated antigens. It is observed that the PTT treatment of GBM-bearing mice activates natural killer cells, CD3+ T cells, CD8+ T cells, and M1 macrophages in the GBM area, increasing the therapeutic efficacy. This study demonstrates that NIR-assisted BK@AIE NPs represent a promising strategy for the improved systematic elimination of GBMs and the activation of local brain immune privilege.

Keywords

glioblastoma; immune response; magnetic resonance; photothermal therapy.

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