CD44细胞
生存素
癌症研究
乳腺癌
透明质酸
癌细胞
靶向治疗
癌症
化学
医学
细胞
内科学
生物化学
解剖
作者
Juan Chen,Jinjin Li,Xiaolu Sun,Huixia Lu,Kuai Liu,Zhenbo Li,Jianyue Guan,Huiling Song,Wei Wei,Yanhong Ge,Qiong Fan,Wei Bao,Buyong Ma,Zixiu Du
出处
期刊:Small
[Wiley]
日期:2023-05-08
卷期号:19 (37)
被引量:15
标识
DOI:10.1002/smll.202301043
摘要
Abstract Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome‐based nanocomplexes containing pro‐apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross‐linked nanohydrogels (Herceptin‐HA) to fabricate a HER2/CD44‐targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin‐HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2‐positive SKBR‐3, triple‐negative MDA‐MB‐231, and HER2‐negative drug‐resistant MCF‐7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2‐positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.
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