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具有改善的化疗和光热消融作用的双靶向且pH响应性金纳米棒用于协同癌症治疗

Dual targeted and pH-responsive gold nanorods with improved chemotherapy and photothermal ablation for synergistic cancer treatment.

作者信息

Wang Jing, Wang Hui, Yan Lin, Hu Zhiqiang, Wu Xiuli, Li Fengmei

机构信息

College of Pharmacy, Ningxia Medical University 1160 Shengli Street 750004 Yinchuan China

Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University 659 Shengli Street 750004 Yinchuan China.

出版信息

RSC Adv. 2019 Feb 14;9(10):5270-5281. doi: 10.1039/c8ra09422e. eCollection 2019 Feb 11.

Abstract

Cancer is considered to be one of the leading causes of morbidity and mortality worldwide. A multifunctional nanosystem based on gold nanorods (GNRs) has demonstrated the potential to enhance therapeutic performance. In this research, dual-targeted pH-responsive GNRs for synergistic cancer treatment were developed and investigated. The GNRs could target angiogenic endothelial cells in the tumor region using αvβ3-mediated recognition and subsequently facilitate its specific binding to tumor cells mediated recognition of the folate receptor, which could accumulate precisely at the tumor site. Doxorubicin (DOX) was loaded on to the surface of GNRs a pH-sensitive hydrazone (hz) bond, which could effectively control the drug release by responding to the tumor acidic microenvironment. , the FA/RGD-DOX--GNRs showed higher tumor specificity and killing ability under near-infrared irradiation. Furthermore, in B16-F10 xenograft tumor-bearing mice, FA/RGD-DOX--GNRs produced the optimal tumor therapeutic efficacy by antagonizing angiogenesis, inhibiting cell proliferation and causing necrosis. Therefore, the strategy of integration of a photothermal effect, chemotherapy and a molecular active targeting based double-targeting mode appeared advantageous over chemotherapy or a photothermal therapy alone.

摘要

癌症被认为是全球发病和死亡的主要原因之一。基于金纳米棒(GNRs)的多功能纳米系统已显示出增强治疗效果的潜力。在本研究中,开发并研究了用于协同癌症治疗的双靶向pH响应性GNRs。GNRs可利用αvβ3介导的识别作用靶向肿瘤区域的血管生成内皮细胞,并随后促进其与叶酸受体介导的肿瘤细胞特异性结合,从而可精确地在肿瘤部位积聚。阿霉素(DOX)通过pH敏感的腙(hz)键负载在GNRs表面,该键可通过响应肿瘤酸性微环境有效控制药物释放。此外,FA/RGD-DOX--GNRs在近红外照射下显示出更高的肿瘤特异性和杀伤能力。此外,在携带B16-F10异种移植肿瘤的小鼠中,FA/RGD-DOX--GNRs通过拮抗血管生成、抑制细胞增殖和导致坏死产生了最佳的肿瘤治疗效果。因此,基于光热效应、化疗和分子活性靶向的双靶向模式整合策略似乎比单独的化疗或光热疗法更具优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e61/9060687/a7c8f2472c83/c8ra09422e-f1.jpg

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