Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer

Ther Deliv. 2024;15(11):871-891. doi: 10.1080/20415990.2024.2400044. Epub 2024 Sep 25.

Abstract

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.

Keywords: Nanoparticles; aptamers; breast cancer; modified nanoparticles; siRNA; triple-negative breast cancer.

Plain language summary

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Female
  • Humans
  • Nanoparticles* / chemistry
  • RNA Interference
  • RNA, Small Interfering* / administration & dosage
  • RNA, Small Interfering* / genetics
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / pathology
  • Triple Negative Breast Neoplasms* / therapy

Substances

  • RNA, Small Interfering