Ratiometric combinatorial delivery of docetaxel and erlotinib via folate-functionalized nanostructured lipid carriers for enhanced TNBC treatment.

Triple-negative breast cancer (TNBC) remains an aggressive malignancy with limited therapeutic options. Here, folic acid-functionalized nanostructured lipid carriers (FA-NLCs) containing docetaxel (DOC) or erlotinib (ERL) were evaluated as a combinatorial strategy for TNBC therapy. The FA-DOC-NLCs + FA-ERL-NLCs combination showed IC₅₀ values of 0.68 ± 0.07 and 0.82 ± 0.05 μM in MDA-MB-231 and 4T1 cells, respectively. FA-functionalization enhanced cellular uptake, reactive oxygen species generation, mitochondrial depolarization, apoptosis, and inhibition of colony formation and migration. Pharmacokinetically, DOC Cmax and AUC₀-t increased from 0.30 ± 0.06 to 3.76 ± 0.44 μg/mL and 1.18 ± 0.04 to 51.89 ± 1.78 μg·h/mL, respectively, while ERL Cmax and AUC₀-t increased from 2.93 ± 0.15 to 8.65 ± 0.73 μg/mL and 18.30 ± 0.56 to 117.15 ± 2.31 μg·h/mL. In vivo, the combination enhanced tumor suppression with favorable safety profiles. Collectively, FA-NLCs provide a promising platform for enhancing DOC and ERL therapy in TNBC.