GE11 PEPTIDE-FUNCTIONALIZED LIPOSOMES, CONTAINING CURCUMIN AND DOXORUBICIN FOR THE TREATMENT OF BREAST CÂNCER BY CHEMOTHERAPY

Breast cancer is the most prevalent and lethal among women worldwide, accounting for 30.1% of reported cancer cases in Brazil. Current therapies are often non-selective in treating both primary and metastatic breast cancer, highlighting the need for more effective treatment strategies capable of eradicating tumors. Liposomes offer a promising platform for the encapsulation of antineoplastic agents and other bioactive compounds, which can reduce chemoresistance, enhance drug bioavailability and potency, and enable synergistic therapeutic effects. Furthermore, functionalizing liposomes with DSPE-PEG2000mal conjugated to the GE11 peptide—a ligand of the epidermal growth factor receptor (EGFR), which is overexpressed in solid tumors—represents a targeted strategy to selectively deliver treatments to neoplastic cells, thereby minimizing toxic effects on healthy tissues. Thus, the objective of this study is to develop an innovative breast cancer treatment that integrates chemotherapy and nanotechnology. This will be achieved through the development of GE11-functionalized liposomes, containing Doxorubicin (DOX), and Curcumin (CUR), with the aim of promoting tumor cell death and preventing metastasis. In the initial phase of the study, liposomal formulations were developed both with and without conjugation to DSPE-PEG2000mal-G11, encapsulating CUR and DOX. These formulations were characterized using techniques such as DLS, NTA, NMR, FTIR, Cryo-EM. These techniques were employed to assess particle size, PDI, ZP, particle concentration, morphology, and encapsulation efficiency. Drug release kinetics were evaluated, and in vitro cytotoxicity assays were conducted on murine fibroblast cells from areolar connective tissue (L929) and murine mammary adenocarcinoma cells (4T1). The formulations exhibited mean particle diameters ranging from 150 to 280 nm, low polydispersity (PDI < 0.3), particle concentrations on the order of 10¹³ particles/mL, negative zeta potentials (−10 to −12 mV), and spherical morphology. These physicochemical properties remained stable during refrigerated storage (2–8 °C) for up to 120 days. Encapsulation efficiencies were 90% for CUR and 65% for DOX, and the formulations promoted sustained DOX release over a 24-hour period. Preliminary in vitro cytotoxicity assays of the functionalized liposomes demonstrated a generally greater cytotoxic effect against 4T1 (LC₅₀ = 10,5 mM). Therefore, in this initial phase, the liposomal formulations proved to be stable and well-characterized, presenting strong potential.