Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.
Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.
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线粒体靶向氧化石墨烯纳米复合材料用于荧光成像引导的耐药骨肉瘤协同光疗
DOI：
10.1186/s12951-021-00831-6
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发表时间：
2021-03-19
影响因子：
10.2
通讯作者：
Zeng YP
中科院分区：
文献类型：
--
作者：
Zeng WN;Yu QP;Wang D;Liu JL;Yang QJ;Zhou ZK;Zeng YP
骨肉瘤（OS）是儿童和年轻人中最常见的原发性恶性骨肿瘤。耐药性骨肉瘤常常导致化疗失败。因此，治疗耐药骨肉瘤迫切需要针对新治疗靶点的新疗法。线粒体靶向光疗，即协同光动力/光热疗法，已成为治疗耐药肿瘤的一种非常有前途的策略。该研究提出了一种基于近红外成像和多功能石墨烯的新型纳米药物递送系统，该系统可以靶向线粒体并表现出协同光疗作用，并优先在肿瘤中积聚。基于我们之前的研究，（4-羧丁基）三苯基溴化鏻（TPP）（一种线粒体靶向配体）与负载吲哚菁绿（ICG）的聚乙烯亚胺修饰的聚乙二醇化纳米氧化石墨烯片（TPP-PPG@ICG）缀合，以促进细胞内化后线粒体的积累。此后，暴露于单剂量的近红外照射可以实现协同光动力和光热疗法，同时抑制三磷酸腺苷合成和线粒体功能。诱导内在细胞凋亡有助于克服耐药性并导致肿瘤细胞死亡。经过荧光成像引导的协同光疗后，线粒体靶向、基于石墨烯的多功能药物递送系统在体外和体内表现出高度选择性的抗癌效率，在携带多柔比星耐药 MG63 肿瘤细胞的小鼠中显着抑制肿瘤进展，且没有明显的毒性。线粒体靶向的TPP-PPG@ICG纳米复合材料构成了一类用于荧光成像引导的协同光疗的新型纳米药物，并显示出治疗耐药骨肉瘤的前景。在线版本包含可在 10.1186/s12951-021-00831-6 获取的补充材料。
Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma. The online version contains supplementary material available at 10.1186/s12951-021-00831-6.
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影响因子：
10.8
作者：
Lu, Phong;Bruno, Benjamin J.;Lim, Carol S.
通讯作者：
Lim, Carol S.
DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
线粒体靶向磁性复合纳米粒子用于增强癌症光疗
影响因子：
13.3
作者：
Guo, Ranran;Peng, Haibao;Yang, Wuli
通讯作者：
Yang, Wuli
影响因子：
3.2
作者：
Aranda, A.;Sequedo, L.;Gombau, L.
通讯作者：
Gombau, L.
影响因子：
17.1
作者：
Marcano, Daniela C.;Kosynkin, Dmitry V.;Tour, James M.
通讯作者：
Tour, James M.