Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer
Creators: name: Sai, Boya Manasa
name: Dinakar, Yirivinti Hayagreeva
name: Kumar, Hitesh
name: Jain, Rupshee
name: Kesharwani, Sharyu
name: Kesharwani, Siddharth S
name: Mudavath, Shyam lal
name: Ramkishan, Ajmeer
name: Jain, Vikas
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Space Science
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: 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. Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, have prompted attention to alternate approaches to address these difficulties. RNA interference (RNAi) by small interfering RNA (siRNA) is one such approach, which 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 many hurdles that hinder the desired biological activity of naked siRNA. For addressing various problems pertaining to the delivery of naked siRNA, nanoparticles are employed to carry siRNA to the target cells. We have attempted to outline a broad variety of nanocarriers carrying various siRNAs developed for the therapy of breast cancer and triple-negative breast cancer. RNA interference by small interfering RNA (siRNA) is a promising approach to treat cancer. siRNA can quickly modify and suppress the expression of the target gene. Naked siRNA is unstable hence requires novel delivery platforms. Site-specific delivery of siRNA is possible through smart nanocarriers. Various polymeric, metallic, lipid-based nanoparticles were explored to deliver siRNA. Nanocarriers prevent degradation and enhanced therapeutic efficacy of loaded siRNA. siRNA loaded nanoparticles and its effect against breast cancer are discussed. siRNA in combination with either drugs or other siRNAs demonstrated better effects. Enhanced uptake and serum stability were observed with modified nanosystems. Nanocarriers modified using various ligands demonstrate better anti-cancer effects. Various smart nanocarriers with distinct characteristics facilitate the release of siRNA at the target site. Studies demonstrating the effectiveness of siRNA in triple-negative breast cancer, an aggressive form of breast cancer were summarised in this section. The quantum dot-lipid nanocarriers and aptamer functionalized nanocarriers with their anti-cancer effects were briefly discussed. siRNA loaded nanocarriers demonstrated anti-angiogenetic effects, controlled metastasis and targeted stem cells associated with breast cancer. Various <i>in vitro</i> and <i>in vivo</i> models were employed to exploit the mechanisms involved in cancer progression. siRNA based therapies demonstrated effectiveness in various models of breast cancer. Limited clinical translation could be attributed to several challenges. Addressing these challenges would lead to successful clinical translation.