Hyaluronic acid-engineered NLCs as a macromolecular delivery platform for APOBEC3B siRNA and gemcitabine in triple-negative breast cancer: In vitro to in ovo assay

Triple-negative breast cancer (TNBC) lacks targetable receptors and has poor clinical outcomes. This study combines hyaluronic acid (HA), a CD44-binding glycosaminoglycan, with APOBEC3B siRNA to engineer HA-functionalised nanostructured lipid carriers (HA-NLCs) that co-deliver gemcitabine hydrochloride (Gem HCl) and APOBEC3B siRNA to MDA-MB-231 TNBC cells. Of the four ON-TARGET plus APOBEC3B siRNA duplexes, siRNA-C gave the highest silencing (97.7% mRNA knockdown) and was selected for encapsulation. NLC entrapment (EE 68.29%) preserved its activity (97.0% suppression). The Box-Behnken-optimised Gem HCl: siRNA-NLCs measured 188.2 nm (PDI 0.284, ZP -3.30 mV). HA coating at a 3:1 NLC: HA ratio produced stable HA-NLCs (278 nm, PDI 0.137, ZP -35.3 mV), confirming successful surface functionalization and colloidal stability. Gem HCl: APOBEC3B siRNA-NLC showed the strongest cytotoxicity, enhanced apoptosis and G2.M arrest. HA-Gem HCl: APOBEC3B siRNA-NLCs showed sustained, progressive apoptotic activity, attributed to combined drug-gene therapy and HA-mediated CD44 receptor internalisation. In the chick chorioallantoic membrane (CAM) tumour model, H&E staining revealed treatment-associated histological changes, including areas consistent with necrosis, reduced tumour cellularity and altered tissue architecture. These preliminary findings warrant further quantitative validation. Overall, these findings highlight the potential of HA-coated NLCs as a platform for co-delivering gemcitabine and APOBEC3B siRNA in TNBC, warranting further mechanistic and therapeutic evaluation.

Abstract from PubMed (PMID 43000064). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.