Construction of Urokinase-Type Plasminogen Activator Receptor-Targeted Heterostructures for Efficient Photothermal Chemotherapy against Cervical Cancer To Achieve Simultaneous Anticancer and Antiangiogenesis
Construction of Urokinase-Type Plasminogen Activator Receptor-Targeted Heterostructures for Efficient Photothermal Chemotherapy against Cervical Cancer To Achieve Simultaneous Anticancer and Antiangiogenesis
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尿激酶型纤溶酶原激活剂受体靶向异质结构的构建，用于宫颈癌的高效光热化疗，以实现同时抗癌和抗血管生成
DOI：
10.1021/acsami.9b15751
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发表时间：
2019-10-30
影响因子：
9.5
通讯作者：
Zhu, Xueqiong
中科院分区：
文献类型：
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作者：
Hu, Xiaoli;Mandika, Chetry;Zhu, Xueqiong
根据宫颈癌的临床特点，合理设计和构建治疗性纳米药物是实现肿瘤精准治疗的重要策略。在此，我们制造了一种靶向宫颈癌的金纳米棒-介孔二氧化硅异质结构，用于协同递送顺铂和抗血管生成药物阿瓦斯汀（cisplatin-AuNRs@SiO2-Avastin@PEI/AE105），以实现协同化学光热治疗。基于数据库分析和临床样品染色，结合ae105靶向肽明显提高了纳米系统的细胞内摄取，增强了宫颈癌细胞与正常细胞之间的杀伤能力和选择性。也可用于特异性监测临床宫颈标本中尿激酶型纤溶酶原激活物受体（uPAR）的表达水平，作为肿瘤治疗预后的早期指标。在808 nm激光照射下，纳米系统通过诱导活性氧过度产生介导的细胞凋亡，表现出智能nir光触发药物释放和突出的光动力学活性。纳米系统还可以同时抑制HeLa肿瘤的生长和血管生成，在主要器官中没有明显的组织学损伤。总之，本研究不仅为宫颈癌的精准治疗和临床快速诊断提供了一种基于临床数据的智能纳米药物的合理设计策略，而且有助于纳米药物临床翻译的发展。
Rational design and construction of theranostic nano medicines based on clinical characteristics of cervical cancer is an important strategy to achieve precise cancer therapy. Herein, we fabricate a cervical cancer-targeting gold nanorod-mesoporous silica heterostructure for codelivery of synergistic cisplatin and antiangiogenic drug Avastin (cisplatin-AuNRs@SiO2-Avastin@PEI/AE105) to achieve synergistic chemophotothermal therapy. Based on database analysis and clinical sample staining, conjugation of the AE105-targeting peptide obviously improves the intracellular uptake of the nanosystem and enhances the cancer-killing ability and selectivity between cervical cancer and normal cells. It could also be used to specifically monitor the urokinase-type plasminogen activator receptor (uPAR) expression level in clinical cervical specimens, which would be an early indicator of prognosis in cancer treatment. Under 808 nm laser irradiation, the nanosystem demonstrates smart NIR-light-triggered drug release and prominent photodynamic activity via induction of reactive oxygen species overproduction-mediated cell apoptosis. The nanosystem also simultaneously suppresses HeLa tumor growth and angiogenesis in vivo, with no evident histological damage observed in the major organs. In short, this study not only provides a clinical data-based rational design strategy of smart nanomedicine for precise treatment and rapid clinical diagnosis of cervical cancer but also contributes to the development of the clinical translation of nanomedicines.