Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy.
Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy.
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DOI：
10.1136/jitc-2022-006226
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发表时间：
2023-01
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
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作者：
高强度聚焦超声（High-intensity focused ultrasound， HIFU）在治疗实体肿瘤方面显示出相当大的前景，但其超声能量容易衰减，导致靶区能量积累不足。此外，单纯HIFU消融不可避免地会导致残留肿瘤的存在，从而导致肿瘤复发和转移。在这里，我们描述了一种基于新型载氧仿生全氟碳纳米颗粒（M@P-SOP）的HIFU促进与免疫调节相结合的协同方案，以刺激肿瘤细胞中的免疫原性细胞死亡，同时减轻免疫抑制肿瘤微环境。采用双乳化挤膜法制备M@P-SOP。通过HIFU联合免疫治疗，评价M@P-SOP对临床前移植4T1肿瘤模型的抗癌和抗转移作用。利用流式细胞术和免疫荧光技术阐明HIFU+M@P-SOP的潜在机制及其在抗程序性死亡配体-1 （PD-L1）治疗中的作用。在光声/MR/超声（US）多模态成像引导下，M@P-SOP在肿瘤中大量富集，大大增强了HIFU对肿瘤组织的原位杀伤，诱导更强的肿瘤免疫原性细胞死亡，刺激树突状细胞成熟，活化CD8+ T细胞。同时M@P-SOP释放氧气缓解肿瘤缺氧环境，使肿瘤m2型巨噬细胞重极化为抗肿瘤m1型。同时进行抗pd - l1治疗，抗肿瘤免疫反应进一步扩大到全身，模拟远处肿瘤的生长得到有效抑制。我们的研究结果提供了一种非常有前途的HIFU增效剂，可以有效改善声学和缺氧环境，最终通过刺激HIFU消融下宿主的抗肿瘤免疫来抑制肿瘤的生长和转移，特别是与PD-L1抗体免疫治疗协同。
High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment. M@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy. Guided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU’s killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8+ T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed. Our findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host’s antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy.
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DOI：
10.3389/pore.2021.1609802
发表时间：
2021
期刊：
Pathology oncology research : POR
影响因子：
--
作者：
Sebestyén A;Kopper L;Dankó T;Tímár J
通讯作者：
Tímár J
影响因子：
10.9
作者：
Abe S;Nagata H;Crosby EJ;Inoue Y;Kaneko K;Liu CX;Yang X;Wang T;Acharya CR;Agarwal P;Snyder J;Gwin W;Morse MA;Zhong P;Lyerly HK;Osada T
通讯作者：
Osada T
影响因子：
4.6
作者：
Fite BZ;Wang J;Kare AJ;Ilovitsh A;Chavez M;Ilovitsh T;Zhang N;Chen W;Robinson E;Zhang H;Kheirolomoom A;Silvestrini MT;Ingham ES;Mahakian LM;Tam SM;Davis RR;Tepper CG;Borowsky AD;Ferrara KW
通讯作者：
Ferrara KW
仿生聚合物磁性纳米载体极化肿瘤相关巨噬细胞，用于增强免疫治疗
影响因子：
13.3
作者：
Liu, Lingqiao;Wang, Yi;Zhou, Shaobing
通讯作者：
Zhou, Shaobing
DOI：
10.1109/tuffc.2011.1869
发表时间：
2011-04-01
影响因子：
3.6
作者：
Chen, Wen-Shiang;Shen, Che-Chou;Yeh, Chih-Kuang
通讯作者：
Yeh, Chih-Kuang