Acid-Triggered Charge-Convertible Graphene-Based All-in-One Nanocomplex for Enhanced Genetic Phototherapy of Triple-Negative Breast Cancer.,Advanced Healthcare Materials

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Acid-Triggered Charge-Convertible Graphene-Based All-in-One Nanocomplex for Enhanced Genetic Phototherapy of Triple-Negative Breast Cancer.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2019-12-04 , DOI: 10.1002/adhm.201901187
Chunhui Wu _{1,

2} , Yuan Tian ₁ , Yingxue Zhang ₁ , Jiming Xu ₁ , Yikun Wang ₁ , Xiaotian Guan ₁ , Tingting Li _{1,

2} , Hong Yang _{1,

2} , Shun Li _{1,

2} , Xiang Qin _{1,

2} , Yiyao Liu _{1,

2,

3}

Affiliation

Highly efficient and stimulus-responsive nanomedicines for cancer treatment are currently receiving tremendous attention. In this study, an acid-triggered charge-reversible graphene-based all-in-one nanocomplex is appropriately designed by surface modification with multilayer polymers and simultaneous co-transportation of photosensitizer indocyanine green (ICG) and oligonucleotide inhibitor of miR-21 (miR-21i) to achieve highly efficient genetic phototherapy in a controlled manner. The nanocomplex (denoted as GPCP/miR-21i/ICG) effectively protects miR-21i from degradation and exhibits excellent photothermal/photochemical reactive oxygen species (ROS) generation as well as fluorescence imaging ability. The cargoes ICG and miR-21i can significantly be released at acidic pH compared with normal physiological medium and escaped from endosomes/lysosomes due to the acid-triggered charge reversal effect. Typically, the released miR-21i downregulate the endogenous miR-21 and result in the upregulation of the target proteins PTEN and Bax, thus increasing the phototherapeutic efficiency of ICG. High in vivo anticancer efficiency against the MDA-MB-231 triple-negative breast cancer (TNBC) model is obtained due to the combination of genetic regulation of miR-21i and the photokilling effect of ICG. This work highlights the great potential of this smart nanocomplex as an attractive modality of gene-photo combined treatment of cancer, especially for intractable TNBC.

中文翻译：

酸引发的电荷可转换石墨烯基多合一纳米复合物，用于三阴性乳腺癌的增强遗传光疗。

用于癌症治疗的高效且对刺激有反应的纳米药物目前正受到极大关注。在这项研究中，通过与多层聚合物进行表面改性，并同时光敏剂吲哚花青绿（ICG）和miR-21（miR -21i）以可控的方式实现高效的遗传光疗。纳米复合物（表示为GPCP / miR-21i / ICG）可有效保护miR-21i免受降解，并表现出出色的光热/光化学活性氧（ROS）生成以及荧光成像能力。与正常的生理介质相比，ICG和miR-21i货物可在酸性pH下显着释放，并且由于酸触发的电荷逆转作用而从内体/溶酶体中逸出。通常，释放的miR-21i下调内源性miR-21，并导致靶蛋白PTEN和Bax上调，从而提高ICG的光疗效率。由于miR-21i的遗传调控和ICG的光杀灭作用相结合，因此获得了针对MDA-MB-231三阴性乳腺癌（TNBC）模型的高体内抗癌效率。这项工作强调了这种智能纳米复合物作为基因-光联合治疗癌症的一种有吸引力的方式的巨大潜力，特别是对于顽固性TNBC。释放的miR-21i下调内源性miR-21，并导致靶蛋白PTEN和Bax上调，从而提高了ICG的光疗效率。由于miR-21i的遗传调控和ICG的光杀灭作用相结合，因此获得了针对MDA-MB-231三阴性乳腺癌（TNBC）模型的高体内抗癌效率。这项工作强调了这种智能纳米复合物作为基因-光联合治疗癌症的一种有吸引力的方式的巨大潜力，特别是对于顽固性TNBC。释放的miR-21i下调内源性miR-21，并导致靶蛋白PTEN和Bax上调，从而提高了ICG的光疗效率。由于miR-21i的遗传调控和ICG的光杀灭作用相结合，因此获得了针对MDA-MB-231三阴性乳腺癌（TNBC）模型的高体内抗癌效率。这项工作强调了这种智能纳米复合物作为基因-光联合治疗癌症的一种有吸引力的方式的巨大潜力，特别是对于顽固性TNBC。由于miR-21i的遗传调控和ICG的光杀灭作用相结合，因此获得了针对MDA-MB-231三阴性乳腺癌（TNBC）模型的高体内抗癌效率。这项工作突出了这种智能纳米复合物作为基因-光联合治疗癌症的一种有吸引力的方式的巨大潜力，特别是对于顽固性TNBC。由于miR-21i的遗传调控和ICG的光杀灭作用相结合，因此获得了针对MDA-MB-231三阴性乳腺癌（TNBC）模型的高体内抗癌效率。这项工作强调了这种智能纳米复合物作为基因-光联合治疗癌症的一种有吸引力的方式的巨大潜力，特别是对于顽固性TNBC。

更新日期：2020-01-08

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