4.5 Review

Nano-vehicles modulated delivery of therapeutic epigenetic regulators to treat Triple-Negative Breast Cancer

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ELSEVIER
DOI: 10.1016/j.jddst.2022.103924

Keywords

Nano -vehicles; Targeted delivery; Cancer; Nanomedicine; Epigenetic regulators; miRNA; siRNA; HDACIs; DNMTIs

Funding

  1. Consejo Nacional de Ciencia y Tecnologa (CONACyT)
  2. Tecnologico de Monterrey, Mexico under Sistema Nacional de Investigadores (SNI) program
  3. [735340]

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Breast cancer is a disease with different subtypes, including the aggressive triple-negative subtype. Traditional therapies may cause side effects, leading to the exploration of epigenetic regulators for potentially improved treatment of breast cancer. However, challenges like stability and targeting need to be addressed when using these regulators.
Breast cancer (BC) is a disease detected in thousands of women worldwide every year. BC is classified into four subtypes: Luminal A, luminal B, Her2 and triple-negative. The triple-negative (TN) is the most aggressive one, causing a poor prognosis. Traditional therapies such as surgery, chemotherapy, and radiation are usually used as treatment. However, those are not site-directed (exclusive of cancer cells), and they cause damage to adjacent healthy tissues; thus, causing diverse side effects. Nowadays, potential epigenetic regulators including HDAC inhibitors (HDACIs), DNMT inhibitors (DNMTIs), small interfering RNAs (siRNAs) and microRNAs (miRNAs) have been proposed to treat Triple-Negative Breast Cancer (TN-BC), showing excellent results in terms of apoptosis, sensitivity to therapeutic agents, and decreased epithelial mesenchymal transition (EMT) in tumor cells. However, epigenetic regulators exhibit some disadvantage like low stability and high probability of being degraded in the bloodstream. Therefore, researchers have proposed the use of nano-vehicles that are site-directed to transport them to cancer cells, providing a safe environment for epigenetic regulators and avoiding damage to adjacent healthy tissues. In this review, we describe carrier nanoparticles of epigenetic regulators to treat TN-BC tumors. Furthermore, we describe the nanomaterials used for the construction of nano-vehicles, delivery mechanisms, and genes/pathways regulated by epigenetic regulators. Finally, the limitations to overcome in order to apply this type of therapy in the clinic.

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