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肿瘤细胞衍生的细胞外囊泡用于乳腺癌特异性递送治疗性 P53。

Tumor cell-derived extracellular vesicles for breast cancer specific delivery of therapeutic P53.

机构信息

School of Life Science, South China Normal University, Guangzhou 510631, China.

School of Life Science, South China Normal University, Guangzhou 510631, China; MOE Key laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou 510631, China.

出版信息

J Control Release. 2022 Sep;349:606-616. doi: 10.1016/j.jconrel.2022.07.020. Epub 2022 Jul 22.

Abstract

Breast cancer has consistently had the highest incidence among women in the world. Tumor cell-derived extracellular vesicles (EV) have been leveraged as drug carriers for cancer treatment. Herein, we developed an efficient theranostic platform for breast cancer-specific delivery of lipophilic triphenylphosphonium (TPP)-modified therapeutic recombinant P53 proteins (TPP/P53) by breast cancer cell-derived EVs. We observed that the EVs were routinely captured by their patent cells, so when, TPP/P53 was loaded into the EVs (TPP/P53@EVs), TPP/P53 was targeted to the mitochondria of breast cancer cells, where it caused signal amplification and induced the death of breast cancer cells. Our findings demonstrated that the TPP/P53@EVs showed good tumor-targeting capability and efficiently destroyed the tumor tissues without any obvious toxicity in vivo. Therefore, our TPP/P53@EVs might provide a "drug-free" strategy for future applications in breast cancer therapy.

摘要

乳腺癌在全球女性中发病率一直居高不下。肿瘤细胞衍生的细胞外囊泡(EV)已被用作癌症治疗的药物载体。在此,我们通过乳腺癌细胞衍生的 EV 开发了一种用于亲脂性三苯基膦(TPP)修饰的治疗性重组 P53 蛋白(TPP/P53)的高效治疗学平台,用于乳腺癌的特异性递药。我们观察到 EV 被其亲本细胞常规捕获,因此当 TPP/P53 被装载到 EV 中(TPP/P53@EVs)时,TPP/P53 被靶向到乳腺癌细胞的线粒体,在那里它引起信号放大并诱导乳腺癌细胞死亡。我们的研究结果表明,TPP/P53@EVs 显示出良好的肿瘤靶向能力,并在体内有效地破坏肿瘤组织,而没有明显的毒性。因此,我们的 TPP/P53@EVs 可能为未来在乳腺癌治疗中的应用提供一种“无药物”策略。

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