双靶点靶向载药银纳米复合物光热-化疗联合治疗乳腺癌的实验研究

Nowadays, the problems of drug resistance, recurrence and metastasis of breast cancer, the most common malignant cancer in women, are increasingly more serious. It is rather challenging to further improve the therapeutic effect. In this regard, developing new treatment strategies should be especially considered. A large number of studies have shown that cancer stem cells play a key role in cancer recurrence, metastasis and therapy resistance, silver nanoparticles and chemotherapy have a synergistic effect in the treatment of cancer, and triangular silver nanoparticles have excellent photothermal property. In this study, we will construct double-targeted targeting (e.g., breast cancer cells and breast cancer stem cells) and double synergistic (e.g., synergistic effects of silver nanoparticles and chemotherapy, photothermal therapy and chemotherapy) drug-loaded triangular silver nanocomposites. The pharmacokinetics, biocompatibility, targeting ability and the in vivo distribution of the nanocomposites, the in vitro/in vivo inhibitory effects on breast cancer and the molecular mechanisms of the combined photothermal-chemotherapy will be investigated. Our study will provide new methods and ideas for the treatment of breast cancer.

乳腺癌是女性最常见的恶性肿瘤，耐药和复发转移现象日益严重，如何进一步提升治疗效果面临着重大挑战，还需要开发新的治疗策略。大量证据表明：肿瘤干细胞在肿瘤的复发、转移和治疗抵抗中起着关键性作用；纳米银有化疗协同效应，而三角形纳米银还具有良好的光热性能。因此我们拟构建一种双靶点靶向（乳腺癌细胞和乳腺癌干细胞）和双重协同作用（纳米银化疗协同和光热-化疗协同）的载药三角形银纳米复合物。评价该复合物的药动学及生物安全性，研究其靶向特异性、体内生物分布、体内/体外光热疗联合化疗抑制乳腺癌的效应及相关分子机制，为乳腺癌的治疗提供新的方法和思路。

乳腺癌是现今全球女性发病率最高的恶性肿瘤，具有年轻化、恶性程度及死亡率高等特点。复发和转移是乳腺癌治疗失败的主要原因，严重威胁着患者的生命健康。如何增强疗效，有效提高乳腺癌患者的存活率，一直是临床上亟待解决的难题。. 本研究旨在构建一种双靶点靶向和双重协同作用的多功能载药三角形银纳米复合物，探讨其体内外治疗乳腺癌的有效性，并研究协同抑癌作用的可能机制。. 本研究结果发现：. 1. 银纳米复合物与阿霉素联合展现出最强的广谱抗乳腺癌协同效应；. 2. 构建的双靶向载药银纳米复合物具有良好的生物相容性和光热性能，并可高效靶向乳腺癌细胞和乳腺癌干细胞；. 3. 双靶向载药银纳米复合物联合激光照射通过纳米银与化疗以及化疗与光热治疗的双重协同作用显著抑制了乳腺癌的生长和转移； . 4. 双靶向载药银纳米复合物联合激光照射通过活性氧的产生和细胞外信号调节激酶1/2信号通路的激活发挥其协同抑制乳腺癌作用。. 本研究将为多功能抗肿瘤高效靶向纳米试剂的研发提供借鉴和参考。