Folate-Targeted Curcumin Nanoliposomes for Receptor- Mediated Delivery in Triple-Negative Breast Cancer Cells

Abstract

Introduction: Curcumin has reported anticancer activity, but its poor aqueous solubility, limited bioavailability, and relatively low intrinsic potency restrict its therapeutic translation. This study developed folate-conjugated PEGylated curcumin nanoliposomes (FA-Lipo-Cur) to improve curcumin delivery to folate receptor–positive MDA-MB-231 triple-negative breast cancer cells.

Methods: Curcumin-loaded liposomes were prepared by thin-film hydration followed by post-insertion of DSPE-PEG(2000)-folate. The formulations were characterized for particle size, polydispersity index, ζ-potential, morphology, encapsulation efficiency, and in vitro release. Cytotoxicity was evaluated by MTT assay after 48 h exposure to free curcumin, non-targeted Lipo-Cur, and FA-Lipo-Cur. Blank liposomes and a concentration-dependent folate receptor-blocking assay were included to assess carrier-related toxicity and targeting specificity.

Results: Both liposomal formulations showed predominantly spherical morphology, acceptable size distribution, negative ζ-potential, and high curcumin encapsulation. FA-Lipo-Cur had a mean size of 218 ± 8.6 nm, PDI of 0.17 ± 0.03, ζ-potential of −28.4 ± 2.3 mV, and encapsulation efficiency of 81.6 ± 2.8%. Both formulations showed sustained curcumin release over 50 h, with FA-Lipo-Cur exhibiting slower release than Lipo-Cur. FA-Lipo-Cur produced the lowest IC₅₀ value (33 ± 3.3 μg/mL), followed by Lipo-Cur (48 ± 3.9 μg/mL) and free curcumin (60 ± 4.1 μg/mL). Folate receptor blocking increased the IC₅₀ of FA-Lipo-Cur to 46.5 ± 3.2 μg/mL and progressively increased cell viability in the concentration-dependent blocking assay.

Conclusion: FA-Lipo-Cur improved curcumin delivery and in vitro cytotoxic activity in MDA-MB-231 cells, with evidence supporting partial folate receptor-mediated uptake. These findings support further investigation of FA-Lipo-Cur as an adjunctive or combination-oriented nanocarrier platform rather than as a replacement for standard chemotherapy.