Nanoparticles for co-delivery of paclitaxel and curcumin to overcome chemoresistance against breast cancer

Abstract

As a prominent cause of morbidity and mortality in women, breast cancer continues to be challenging to treat due to the lack of effective drugs. Paclitaxel (PTX) is an effective chemotherapeutic agent for treating breast cancer patients. The effectiveness of PTX against breast cancer is nevertheless diminished by multidrug resistance (MDR). In addition to having potent reversal effects on the MDR brought by PTX in breast cancer, curcumin (CUR) has demonstrated therapeutic and/or adjuvant in treating patients with breast cancer. In this study, amphiphilic di-block copolymer poly(ethylene glycol)-block-poly (lactide-co-glycolide) (PEG-PLGA) was employed for encapsulating PTX and CUR into nanoparticles (PC-NPs) to boost anticancer activity against MDR. The nanoparticles exhibited potential advantages, including a spherical shape, small diameter (85.8 ± 0.21 nm), exceptionally high encapsulation efficiency (83.05 ± 1.35% for PTX and 85.84 ± 0.87% for CUR), and drug loading (38.70 ± 0.97% for PTX and 32.22 ± 0.53% for CUR), a smooth-surface morphology, suitable negative charge (−20.3 ± 1.3 mV), gradient release, and optimum stability. The proliferation of 4T1 and MDA-MB-231 cells implicated in the suppression of the NF-κB signaling pathway was slowed down by PC-NPs. CUR could inhibit the production of P-glycoprotein and reverse MDR in breast cancer cells. Most importantly, CUR and PTX, both in free and nanoparticulate forms, were found to be less toxic on RAW mononuclear macrophages in comparison to both 4T1 and MDA-MB-231 cells. Furthermore, compared to single-nanoparticle formulations, in vivo investigations have revealed that PC-NPs exhibited enhanced tumor suppression and therapeutic outcomes. These findings suggested that PTX and CUR nanoparticle co-delivery is a potentially suitable approach for effectively eradicating breast cancer.