<br>上调具有血液肿瘤屏障渗透性的聚集诱导发射纳米颗粒，用于精确光热消灭脑肿瘤并诱导局部免疫反应,Advanced Materials

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上调具有血液肿瘤屏障渗透性的聚集诱导发射纳米颗粒，用于精确光热消灭脑肿瘤并诱导局部免疫反应
Advanced Materials ( IF 27.4 ) Pub Date : 2021-04-23 , 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

Affiliation

与其他肿瘤相比，胶质母细胞瘤（GBM）极难治疗。近年来，光热疗法（PTT）已显示出先进的治疗效果；然而，由于激光的组织穿透效率相对较低，其在深部肿瘤中的应用仍然具有挑战性。在此，合成了缓激肽（BK）聚集诱导发射纳米颗粒（BK@AIE NPs）；它们可以选择性地穿透血肿瘤屏障 (BTB)，并且在近红外区域 (NIR) 具有很强的吸收性。 T ₁加权磁共振和荧光成像证实，BK配体可以促进BTB腺苷受体激活，从而增强肿瘤内的运输和积累。 BK@AIE NPs在980 nm近红外激光照射下表现出高光热转换效率，有助于治疗深部肿瘤。时空PTT后可有效抑制肿瘤进展，延长小鼠的生存期。近红外辐射可以根除肿瘤组织并释放肿瘤相关抗原。据观察，PTT治疗GBM小鼠可激活GBM区域的自然杀伤细胞、CD3 ⁺ T细胞、CD8 ⁺ T细胞和M1巨噬细胞，提高治疗效果。这项研究表明，NIR 辅助的 BK@AIE NP 代表了一种有前途的策略，可以改善 GBM 的系统消除和激活局部大脑免疫特权。

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

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.

更新日期：2021-06-01

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