siRNA 的治疗递送在乳腺癌和三阴性乳腺癌治疗中的应用。
Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer.
机构信息
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, 570015, India.
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, 570015, India.
出版信息
Ther Deliv. 2024;15(11):871-891. doi: 10.1080/20415990.2024.2400044. Epub 2024 Sep 25.
Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic. When compared with chemotherapy, siRNA has several advantages, including the ability to quickly modify and suppress the expression of the target gene and display superior efficacy and safety. However, there are known challenges and hurdles that limits their clinical translation. Decomposition by endonucleases, renal clearance, hydrophilicity, negative surface charge, short half-life and off-target effects of naked siRNA are obstacles that hinder the desired biological activity of naked siRNA. Nanoparticulate systems such as polymeric, lipid, lipid-polymeric, metallic, mesoporous silica nanoparticles and several other nanocarriers were used for effective delivery of siRNA and to knock down genes involved in breast cancer and triple-negative breast cancer. The focus of this review is to provide a comprehensive picture of various strategies utilized for delivering siRNA, such as combinatorial delivery, development of modified nanoparticles, smart nanocarriers and nanocarriers that target angiogenesis, cancer stem cells and metastasis of breast cancer.
乳腺癌是全球女性癌症相关死亡的主要原因。抗癌药物存在靶向性差、剂量大、对健康细胞有毒性和副作用等问题,这促使人们关注解决这些问题的替代方法。小干扰 RNA(siRNA)的 RNA 干扰就是这样一种策略。与化疗相比,siRNA 具有几个优势,包括能够快速修饰和抑制靶基因的表达,并显示出更好的疗效和安全性。然而,已知的挑战和障碍限制了它们的临床转化。核酸酶分解、肾清除、亲水性、负表面电荷、半衰期短和裸 siRNA 的脱靶效应是阻碍裸 siRNA 发挥预期生物学活性的障碍。纳米颗粒系统,如聚合物、脂质、脂质-聚合物、金属、介孔硅纳米颗粒和其他几种纳米载体,被用于有效递送 siRNA,并敲低与乳腺癌和三阴性乳腺癌相关的基因。本综述的重点是提供各种用于递送 siRNA 的策略的全面描述,如组合递送、改良纳米颗粒的开发、智能纳米载体和靶向血管生成、癌症干细胞和乳腺癌转移的纳米载体。
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