A tumor-targeted nanoplatform with stimuli-responsive cascaded activities for multiple model tumor therapy.,Biomaterials Science

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A tumor-targeted nanoplatform with stimuli-responsive cascaded activities for multiple model tumor therapy.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020/01/15 , DOI: 10.1039/c9bm01992h
Ronghua Jin ₁ , Jirong Xie ₂ , Xiaoshan Yang ₃ , Yu Tian ₁ , Pingyun Yuan ₁ , Yongkang Bai ₁ , Shiyu Liu ₃ , Bolei Cai ₄ , Xin Chen ₁

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Herein, a rambutan-like nanocomplex (PDA-SNO-GA-HA-DOX, PSGHD for short) was designed to enable effective and accurate tumor therapy. The PSGHD nanocomplex consists of an S-nitrosothiol-functionalized polydopamine (PDA-SNO) core and a gambogic acid-derivatized hyaluronic acid (HA-GA) shell with doxorubicin (DOX) as the cargo. Due to the HA section, the PSGHD nanocomplex can be rapidly and selectively internalized by tumor cells instead of healthy cells in 12 h of co-incubation. After that, the internalized PSGHD nanocomplex is able to gradually release both DOX (agent for chemotherapy) and GA (agent for enhancing thermal damage) under different tumor-specific physiological conditions (low pH and rich HAase). When 808 nm NIR radiation was employed, the PSGHD nanocomplex further demonstrated excellent photothermal conversion to increase the local temperature over 43 °C and convert SNO to nitric oxide (NO, an agent for decreasing drug-efflux). Based on the synergistic effects of NO/DOX and GA/heat, the PSGHD nanocomplex simultaneously achieved tumor-specific low-drug-efflux chemotherapy and low-temperature photothermal therapy, resulting in an eight-fold apoptosis of tumor cells over normal cells under NIR radiation. In vivo data from mouse models further showed that the PSGHD nanocomplex can completely inhibit tumor growth and significantly prolong the survival rate of tumor bearing mice in 50 days, demonstrating the high efficiency of the PSGHD nanocomplex for tumor therapy.

中文翻译：

具有刺激反应的级联活性的靶向肿瘤的纳米平台，用于多种模型肿瘤治疗。

在本文中，设计了一种红毛丹样纳米复合物（PDA-SNO-GA-HA-DOX，简称PSGHD）以实现有效而准确的肿瘤治疗。PSGHD纳米复合物由S-亚硝基硫醇官能化的聚多巴胺（PDA-SNO）核和藤黄酸衍生的透明质酸（HA-GA）壳组成，并带有阿霉素（DOX）。由于具有HA部分，在共孵育12小时后，PSGHD纳米复合物可以被肿瘤细胞而不是健康细胞快速选择性地内化。之后，内化的PSGHD纳米复合物能够在不同的肿瘤特异性生理条件（低pH值和富HAase）下逐渐释放DOX（化学治疗剂）和GA（增强热损伤剂）。当采用808 nm NIR辐射时，PSGHD纳米复合物进一步展示了出色的光热转化能力，可将局部温度提高到43°C以上，并将SNO转化为一氧化氮（NO，一种降低药物外流的试剂）。基于NO / DOX和GA /热的协同作用，PSGHD纳米复合物同时实现了肿瘤特异性的低药流化疗和低温光热疗法，在NIR下导致肿瘤细胞的凋亡是正常细胞的八倍。辐射。小鼠模型的体内数据进一步表明，PSGHD纳米复合物可以完全抑制肿瘤的生长，并显着延长荷瘤小鼠在50天的存活率，证明了PSGHD纳米复合物用于肿瘤治疗的高效性。基于NO / DOX和GA /热的协同作用，PSGHD纳米复合物同时实现了肿瘤特异性的低药流化疗和低温光热疗法，在NIR下导致肿瘤细胞的凋亡是正常细胞的八倍。辐射。小鼠模型的体内数据进一步表明，PSGHD纳米复合物可以完全抑制肿瘤的生长，并显着延长荷瘤小鼠在50天的存活率，证明了PSGHD纳米复合物用于肿瘤治疗的高效性。基于NO / DOX和GA /热的协同作用，PSGHD纳米复合物同时实现了肿瘤特异性的低药流化疗和低温光热疗法，在NIR下导致肿瘤细胞的凋亡是正常细胞的八倍。辐射。小鼠模型的体内数据进一步表明，PSGHD纳米复合物可以完全抑制肿瘤的生长，并显着延长荷瘤小鼠在50天的存活率，证明了PSGHD纳米复合物用于肿瘤治疗的高效性。

更新日期：2020-03-31

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