Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, P. R. China.
Department of Radiology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230001, P. R. China.
Adv Sci (Weinh). 2022 Nov;9(32):e2204067. doi: 10.1002/advs.202204067. Epub 2022 Sep 8.
Cancer photo-immunotherapy (CPIT) as an ideal strategy can rapidly release hostile signals by appropriate dosage of focal laser irradiation to unmask primary tumor immunogenicity and can activate adaptive immunity to control distant metastases. However, many factors, including disordered immunometabolism, poor penetration of photothermal agents and immuno-regulators, inadequate laser penetration into the deep tumor region, restrict the therapeutic outcomes of CPIT. Here, a second near-infrared window (NIR-II) photo-immunometabolic cancer therapy (PICT) by a programmed raspberry-structured nanoadjuvant (PRN ) is presented that can potentiates efficient immunogenic cell death (ICD) in deep tumor tissue and alleviates immunometabolic disorder. The PRN is architected through self-assembly of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor modified small-sized CuS nanoparticles (CuS ) and tumor microenvironment (TME) responsive cationized polymeric matrix. The TME can trigger the splitting and surface cationization of PRN into small cationized CuS that feature high transcytosis potential and TME immunometabolic regulation. Upon NIR-II irradiation, CuS induce homogeneous ICD and release immunometabolic regulator in deep tumor tissues, which ameliorates IDO-1 mediated immunometabolic disorder and further suppresses regulatory T cells infiltration. PRN mediated PICT effectively delays the primary murine mammary carcinoma 4T1 tumor growth and inhibits the lethal pulmonary metastasis in combination with programmed cell death protein 1 (PD1) blockade.
癌症光免疫疗法（CPIT）是一种理想的策略，可以通过适当剂量的焦点激光照射迅速释放敌对信号，揭示原发性肿瘤的免疫原性，并激活适应性免疫以控制远处转移。然而，许多因素，包括免疫代谢紊乱、光热剂和免疫调节剂的渗透不良、激光对深部肿瘤区域的穿透不足，限制了 CPIT 的治疗效果。在这里，提出了一种通过编程树莓结构纳米佐剂（PRN）的二次近红外窗口（NIR-II）光免疫代谢癌症治疗（PICT），可以增强深部肿瘤组织中有效的免疫原性细胞死亡（ICD），并缓解免疫代谢紊乱。PRN 通过吲哚胺 2,3-双加氧酶 1（IDO-1）抑制剂修饰的小尺寸 CuS 纳米颗粒（CuS）和肿瘤微环境（TME）响应的阳离子聚合物基质的自组装构建而成。TME 可以触发 PRN 的分裂和表面阳离子化，形成具有高转胞作用和 TME 免疫代谢调节能力的小阳离子化 CuS。在 NIR-II 照射下，CuS 在深部肿瘤组织中诱导同质 ICD 并释放免疫代谢调节剂，改善 IDO-1 介导的免疫代谢紊乱，并进一步抑制调节性 T 细胞浸润。PRN 介导的 PICT 与程序性细胞死亡蛋白 1（PD1）阻断联合有效地延迟了原发性小鼠乳腺肿瘤 4T1 的生长，并抑制了致命的肺转移。
