Folic acid-modified curcumin-loaded liposomes for breast cancer therapy

Breast cancer is the commonest cancer among women, with more than 2 million cases per year and a lethality rate of 17.7%. The treatment of breast cancer still being a challenge due to the high heterogeneity of tumor cells. In this scenario, the development of targeted nanosystems for drug delivery has been investigated. Thus, the aim of this study was the development and characterization of folic acid-modified curcumin-loaded liposomes (LIP-CCM-FA) for the treatment of breast cancer. For this purpose, LIP-CCM-FA and unmodified liposomes (LIP-CCM) were developed and characterized in vitro using MCF-7 cells culture in two-dimensional (2D) and three-dimensional (3D) models. LIP-CCM and LIP-CCM-FA showed low particles size (~ 138 nm), narrow polydispersity indexes (~ 0.140), negative zeta potential (~ −13 mV), and high drug encapsulation efficiency (> 73%). Furthermore, LIP-CCM-FA showed a significantly greater cytotoxicity effect when compared with free curcumin and LIP-CCM using 2D and 3D cell culture models. In addition, in vitro cellular uptake assays using 2D and 3D models indicated higher cellular internalization and spheroid penetration of LIP-CCM-FA when compared with free curcumin and LIP-CCM, suggesting the potential of folic acid modification for improving drug internalization in breast cancer cells through its recognition by folate receptors overexpressed. In summary, this novel nanosystem demonstrated a greater in vitro antitumoral effect due to its ability to permeate tissues and be specifically recognized by folate receptors.