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

Ming Zhang, Wentao Wang*, Mohsen Mohammadniaei, Tao Zheng, Qicheng Zhang, Jon Ashley, Shunjie Liu, Yi Sun, Ben Zhong Tang

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
Article number2008802
JournalAdvanced Materials
Number of pages12
ISSN0935-9648
DOIs
Publication statusAccepted/In press - 2021

Bibliographical note

Funding Information:
This work was supported by the Villum Fonden, Denmark (Project No. 13153) and National Natural Science Foundation of China, Basic Science Center Program (51988102). The authors are also grateful for the financial support from the Research Grant Council of Hong Kong (Grant Nos. 16305518 and C6009‐17G). All animal operations were carried out in accordance with institutional animal use and care regulations provided by Nanjing Normal University.

Keywords

  • Glioblastoma
  • Immune response
  • Magnetic resonance
  • Photothermal therapy

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