Light-Triggered Retention and Cascaded Therapy of Albumin-Based Theranostic Nanomedicines to Alleviate Tumor Adaptive Treatment Tolerance
Light-Triggered Retention and Cascaded Therapy of Albumin-Based Theranostic Nanomedicines to Alleviate Tumor Adaptive Treatment Tolerance
复制标题
基于白蛋白的治疗诊断纳米药物的光触发保留和级联治疗可减轻肿瘤适应性治疗耐受性
DOI：
10.1002/adfm.201707291
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发表时间：
2018-04-25
影响因子：
19
通讯作者：
Liang, Xing-Jie
中科院分区：
文献类型：
--
作者：
Chen, Jing;Liu, Lu;Liang, Xing-Jie
与化疗相关的肿瘤适应性治疗耐受源于低肿瘤蓄积和不良反应，并且仍然是癌症治疗的巨大挑战。本文中，开发了用二氮丙啶修饰并负载吲哚菁绿色（ICG）和替拉扎明（TPZ）的基于人血清白蛋白（HSA）的纳米药物，表示为ICG/TPZ@HSA dNM。所获得的ICG/TPZ@HSA dNM可以通过由激光在肿瘤区域中的顺序照射触发的级联协同事件来有效地根除肿瘤。在405 nm激光照射下，ICG/TPZ@HSA dNM能够通过交联形成聚集体，从而实现增强的肿瘤部位蓄积和延长的保留时间。随后用808 nm激光照射肿瘤区域产生局部高热和活性氧，这导致有效的肿瘤消融和肿瘤微环境中局部缺氧的增加。由此产生的局部缺氧进一步将最初无毒的TPZ活化为高度细胞毒性的衍生物，通过该衍生物，在光疗后实现精确的生物活化化疗。因此，在激光照射时，成功地触发了聚集、光疗和生物活化化学疗法的级联，这实现了肿瘤的有效精确根除，而没有体内可检测的副作用。
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.