Targeted polymer lipid hybrid nanoparticles for in-vitro siRNA therapy in triple-negative breast cancer

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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, characterised by a lack of hormone receptors and HER2 expression, resulting in limited treatment options and poor patient outcomes. This study explores a novel therapeutic approach using PLGA lipid nanoparticles loaded with siXBP1 and conjugated with an epidermal growth factor receptor (EGFR) antibody. This nanncarrier will silence the XBP1 gene, which is crucial for the progression and survival of TNBC, particularly in hypoxic conditions. The conjugation of nanoparticles with the EGFR antibody improves their targeting ability to TNBC cells, as confirmed by confocal microscopy and flow cytometry. The fluorescence intensity of the targeted nanoparticles was 1.45 times higher than that of the non-targeted counterparts. These nanoparticles efficiently delivered siRNA to TNBC cells, resulting in substantial XBP1 gene silencing efficacy of 75 %. Under hypoxic conditions, this gene silencing effect significantly promoted apoptosis by nearly threefold compared to normoxic conditions. These findings provide valuable insights into targeted therapies for TNBC and pave the way for further in vivo investigations to advance this approach toward clinical applications.