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Light‐Triggered Retention and Cascaded Therapy of Albumin‐Based Theranostic Nanomedicines to Alleviate Tumor Adaptive Treatment Tolerance
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-03-07 , DOI: 10.1002/adfm.201707291 Jing Chen 1 , Lu Liu 2 , Seyed Mohammad Motevalli 2 , Xiaoli Wu 1 , Xiao-Hong Yang 3 , Xianlei Li 2 , Lu Han 3 , Andrea Magrini 4 , Weisheng Guo 2 , Jin Chang 1 , Massimo Bottini 2, 5 , Xing-Jie Liang 2
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-03-07 , DOI: 10.1002/adfm.201707291 Jing Chen 1 , Lu Liu 2 , Seyed Mohammad Motevalli 2 , Xiaoli Wu 1 , Xiao-Hong Yang 3 , Xianlei Li 2 , Lu Han 3 , Andrea Magrini 4 , Weisheng Guo 2 , Jin Chang 1 , Massimo Bottini 2, 5 , Xing-Jie Liang 2
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Tumor adaptive treatment tolerance associated with chemotherapy originates from low tumor accumulation and adverse effects and remains a formidable challenge for cancer therapy. Herein, human serum albumin (HSA)‐based nanomedicines modified with diazirine and loaded with indocyanine green (ICG) and tirapazamine (TPZ), denoted as ICG/TPZ@HSA dNMs are developed. The obtained ICG/TPZ@HSA dNMs can efficiently eradicate the tumors through a cascade of synergistic events triggered by the sequential irradiation of lasers in the tumor area. Upon a 405 nm laser irradiation, the ICG/TPZ@HSA dNMs are able to form aggregates via crosslinking and thus realized enhanced tumor site accumulation and prolonged retention time. The following irradiation at tumor area with an 808 nm laser‐generated local hyperthermia and reactive oxygen species, which results in efficient tumor ablation and increased local hypoxia in the tumor microenvironment. The resulted local hypoxia further activates the initially nontoxic TPZ to a highly cytotoxic derivative, by which precisely bioactivated chemotherapy is achieved following the phototherapy. Thus, upon the laser irradiations, a cascade of aggregation, phototherapy, and bioactivated chemotherapy is successfully triggered, which achieves efficient precise eradication of tumors without detectable side effects in vivo.
中文翻译：
基于白蛋白的治疗性纳米药物的轻触发保留和级联疗法可减轻肿瘤适应性治疗的耐受性
与化学疗法相关的肿瘤适应性治疗耐受性源自低肿瘤积累和不良反应，并且仍然是癌症治疗的巨大挑战。在本文中，开发了使用人脑白蛋白（HSA）的纳米药物，该药物经过重氮嗪修饰并负载了吲哚菁绿（ICG）和替拉帕明（TPZ），称为ICG / TPZ @ HSA dNMs。所获得的ICG / TPZ @ HSA dNM可以通过在肿瘤区域中依次照射激光引发的一系列协同事件来有效根除肿瘤。在405 nm激光照射下，ICG / TPZ @ HSA dNMs能够通过交联形成聚集体，从而实现了增强的肿瘤部位积累和延长的保留时间。随后在808 nm激光产生的局部热疗和活性氧对肿瘤区域的照射下，这导致有效的肿瘤消融并增加了肿瘤微环境中的局部缺氧。产生的局部缺氧进一步将最初无毒的TPZ激活为高度细胞毒性的衍生物，通过光疗后，可以实现精确的生物活化化学疗法。因此，在激光照射下，成功触发了聚集，光疗和生物活化化学疗法的级联，这实现了有效的精确根除肿瘤而没有体内可检测到的副作用。
更新日期：2018-03-07
中文翻译：
基于白蛋白的治疗性纳米药物的轻触发保留和级联疗法可减轻肿瘤适应性治疗的耐受性
与化学疗法相关的肿瘤适应性治疗耐受性源自低肿瘤积累和不良反应，并且仍然是癌症治疗的巨大挑战。在本文中，开发了使用人脑白蛋白（HSA）的纳米药物，该药物经过重氮嗪修饰并负载了吲哚菁绿（ICG）和替拉帕明（TPZ），称为ICG / TPZ @ HSA dNMs。所获得的ICG / TPZ @ HSA dNM可以通过在肿瘤区域中依次照射激光引发的一系列协同事件来有效根除肿瘤。在405 nm激光照射下，ICG / TPZ @ HSA dNMs能够通过交联形成聚集体，从而实现了增强的肿瘤部位积累和延长的保留时间。随后在808 nm激光产生的局部热疗和活性氧对肿瘤区域的照射下，这导致有效的肿瘤消融并增加了肿瘤微环境中的局部缺氧。产生的局部缺氧进一步将最初无毒的TPZ激活为高度细胞毒性的衍生物，通过光疗后，可以实现精确的生物活化化学疗法。因此，在激光照射下，成功触发了聚集，光疗和生物活化化学疗法的级联，这实现了有效的精确根除肿瘤而没有体内可检测到的副作用。
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