Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA.
Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA.
复制标题
利用噬菌体 phi29 衍生的包装 RNA 开发靶向治疗药物以提高三阴性乳腺癌的化疗敏感性
DOI：
10.1186/s12951-020-00758-4
复制
发表时间：
2021-01-07
影响因子：
10.2
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Zhang L;Mu C;Zhang T;Yang D;Wang C;Chen Q;Tang L;Fan L;Liu C;Shen J;Li H
迄今为止，由于靶受体的缺失，三阴性乳腺癌（TNBC）的治疗选择有限，因此只能通过化疗进行治疗。更糟糕的是，TNBC经常对化疗产生耐药性。通过使用小干扰RNA （siRNA）为基础的治疗方法，我们最近的工作证明了x- box结合蛋白1 （XBP1）与人类表皮生长因子受体2阳性（HER2+）乳腺癌的发展和化疗耐药有关。由于siRNA在体内利用和临床转化中的不稳定性、脱靶效应、净负电荷和疏水性，阻碍了其在治疗中的应用。因此，开发一种具有超稳定性和特异性的siRNA给药系统（DDS）是解决siRNA给药困境的必要条件。结果我们基于Phi29 DNA包装马达的3WJ结构组装了RNA耐药纳米RNA （NPs）。为了改善靶向治疗并使TNBC对化疗敏感，RNA NPs配备了靶向适体和XBP1 siRNA的表皮生长因子受体（EGFR）。我们发现我们的RNA NPs在静脉给药后可以减少XBP1的表达并抑制肿瘤的生长。同时，RNA NPs治疗可促进体内化疗增敏，抑制血管生成。结论我们的RNA NPs不仅可以作为siRNA递送的有效平台，还可以作为化疗耐药TNBC治疗的有效平台。
BackgroundTo date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery.ResultsHere, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo.ConclusionsThe results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.
登录
查看更多内容
DOI：
10.1016/j.omtn.2017.10.010
发表时间：
2017-12-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Guo S;Li H;Ma M;Fu J;Dong Y;Guo P
通讯作者：
Guo P
影响因子：
12.4
作者：
Abdelmawla, Sherine;Guo, Songchuan;Li, Qi-Xiang
通讯作者：
Li, Qi-Xiang
影响因子：
17.1
作者：
Liu J;Guo S;Cinier M;Shlyakhtenko LS;Shu Y;Chen C;Shen G;Guo P
通讯作者：
Guo P
DOI：
10.1073/pnas.83.24.9373
发表时间：
1986-12-01
影响因子：
11.1
作者：
FREIER, SM;KIERZEK, R;TURNER, DH
通讯作者：
TURNER, DH
影响因子：
64.8
作者：
Chen, Xi;Iliopoulos, Dimitrios;Zhang, Qing;Tang, Qianzi;Greenblatt, Matthew B.;Hatziapostolou, Maria;Lim, Elgene;Tam, Wai Leong;Ni, Min;Chen, Yiwen;Mai, Junhua;Shen, Haifa;Hu, Dorothy Z.;Adoro, Stanley;Hu, Bella;Song, Minkyung;Tan, Chen;Landis, Melissa D.;Ferrari, Mauro;Shin, Sandra J.;Brown, Myles;Chang, Jenny C.;Liu, X. Shirley;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.