Liu Jiuzhou, Ren Shasha, Zhang Xiangyu, Feng Yun, Qiu Zhenglun, Ma Li, Huang Jingwen
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
Department of Breast and Thyroid Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, 471009, People's Republic of China.
Onco Targets Ther. 2021 May 25;14:3429-3442. doi: 10.2147/OTT.S291142. eCollection 2021.
Breast cancer (BC) is the most common type of cancer among women worldwide, and about 30% of males will have recurrent disease.
In order to treat recurrent BC, we designed a type of silica nanodelivery system loaded with epirubicin and curcumin (composite nanoparticles, CNPs). To promote CNPs clinical application, the stability, the blood, immune and cell compatibility, skin stimulation experiments, anti-tumor activity in vivo and in vitro were studied.
In our study, the CNPs had a particle size of 73.9 nm and a uniform size and morphology; moreover, they maintained physical and chemical stability in the blood protein environment. Additionally, results showed that nanoparticles had good blood and immune compatibility, and they did not affect intracellular superoxide dismutase (SOD) and intracellular catalase (CAT). Skin stimulation experiments showed that CNPs did not cause any obvious irritative damage to the intact skin of rabbits. In the cytotoxicity study, CNPs showed strongest antitumor activity. The results of cell cycle and apoptosis studies showed that CNPs could mainly induce apoptosis of S and G2/M phase cells. In vivo, CNPs showed strongest aggregation in the tumor after 6 h of tail vein administration, and a large amount of CNPs continued to accumulate in the blood after 12 h of administration, indicating that CNPs had long circulation ability. The in vivo antitumor activities showed that CNPs had the strongest antitumor activity and tumor targeting ability, and hematoxylin-eosin staining of internal organs showed no obvious difference between treatment groups and negative control.
CNPs have an ideal biosafety and therapeutic effect for recurrent BC, and they have potential clinical application value.
乳腺癌(BC)是全球女性中最常见的癌症类型,约30%的男性会出现复发性疾病。
为了治疗复发性BC,我们设计了一种负载表柔比星和姜黄素的二氧化硅纳米递送系统(复合纳米颗粒,CNPs)。为促进CNPs的临床应用,研究了其稳定性、血液、免疫和细胞相容性、皮肤刺激性实验以及体内外抗肿瘤活性。
在我们的研究中,CNPs的粒径为73.9nm,尺寸和形态均一;此外,它们在血液蛋白环境中保持物理和化学稳定性。另外,结果表明纳米颗粒具有良好的血液和免疫相容性,且不影响细胞内超氧化物歧化酶(SOD)和细胞内过氧化氢酶(CAT)。皮肤刺激性实验表明,CNPs对兔完整皮肤未造成任何明显的刺激性损伤。在细胞毒性研究中,CNPs表现出最强的抗肿瘤活性。细胞周期和凋亡研究结果表明,CNPs主要诱导S期和G2/M期细胞凋亡。在体内实验中,尾静脉给药6小时后,CNPs在肿瘤中显示出最强聚集,给药12小时后,大量CNPs继续在血液中蓄积,表明CNPs具有长循环能力。体内抗肿瘤活性表明,CNPs具有最强的抗肿瘤活性和肿瘤靶向能力,各脏器苏木精-伊红染色显示治疗组与阴性对照组无明显差异。
CNPs对复发性BC具有理想的生物安全性和治疗效果,具有潜在的临床应用价值。