Enhanced Breast Cancer Therapy Using Multifunctional Lipid- Coated Nanoparticles Combining Curcumin Chemotherapy and Nitric Oxide Gas Delivery

Abstract The limitations of conventional treatment modalities for cancer, particularly breast cancer, have promoted the need to develop safer drug delivery systems (DDS). Chemotherapy combined with gas therapy has emerged as an attractive cancer treatment strategy. In this study, curcumin (Cur) loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) were prepared by gas diffusion reaction. A "one-step" ethanol injection method was then used to prepare lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine (LA) to achieve a combination of chemotherapy and NO to enhance the antitumor effect. The prepared Cur-CaCO3@LA-Lip was characterized and evaluated by transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-vis spectrometry, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). TEM observed that the Cur-CaCO3@LA-Lip nanoparticles were subspherical and had a distinct lipid layer covering the periphery. FTIR, XRD, and DSC indicated the successful synthesis of Cur-CaCO3@LA-Lip. Cur-CaCO3@LA-Lip exhibited a large drug loading capacity of 8.89% and 3.1% for Cur and LA, respectively, effectively preventing drug leakage. Furthermore, in vitro and in vivo, Cur-CaCO3@LA-Lip nanoparticles exhibited Cur sustained-release, high cellular uptake, high tumor accumulation, good biocompatibility, robust cytotoxicity, and antitumor efficacy.