Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12274-020-3028-x and is accessible for authorized users.

中文翻译：

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使用多用途黑磷基纳米粒子进行光声免疫治疗。

精确根除原发性肿瘤、对正常组织的副作用最小、抑制转移和防止肿瘤复发的有效治疗策略是抗击癌症的最终目标。我们报告了一种新的治疗策略，它将基于黑磷纳米颗粒的辅助光声 (PA) 疗法与检查点阻断免疫疗法相结合。通过线粒体靶向纳米粒子，PA治疗可以通过PA空化实现线粒体的局部机械损伤，从而实现原发肿瘤的精准根除。更重要的是，PA 疗法可以通过含有 R848 的纳米颗粒作为佐剂产生肿瘤相关抗原，以促进强烈的抗肿瘤免疫反应。当与使用抗细胞毒性 T 淋巴细胞抗原 4 的检查点封锁相结合时，产生的免疫反应将进一步促进浸润的 CD8 和 CD4 T 细胞，以增加 CD8/Foxp3 T 细胞比率，从而抑制远处肿瘤的生长，超出 PA 治疗的直接影响范围。此外，脾脏中检测到的记忆T细胞数量增加，这些细胞抑制肿瘤复发。这种提议的策略提供了对原发性肿瘤的精确根除，并可以诱导长期的肿瘤特异性免疫。电子补充材料补充材料可在 10.1007/s12274-020-3028-x 获取本文的补充材料，授权用户可以访问。脾脏中检测到的记忆T细胞数量增加，这些细胞抑制肿瘤复发。这种提议的策略提供了对原发性肿瘤的精确根除，并可以诱导长期的肿瘤特异性免疫。电子补充材料补充材料可在 10.1007/s12274-020-3028-x 获取本文的补充材料，授权用户可以访问。脾脏中检测到的记忆T细胞数量增加，这些细胞抑制肿瘤复发。这种提议的策略提供了对原发性肿瘤的精确根除，并可以诱导长期的肿瘤特异性免疫。电子补充材料补充材料可在 10.1007/s12274-020-3028-x 获取本文的补充材料，授权用户可以访问。