Co-delivery of berberine and gold nanoparticles on liposomes for photodynamic therapy against 3D lung cancer cells

Abstract

Lung cancer is the second most common cancer diagnosed and is the leading cause of cancer-related deaths globally. Even though there are established lung cancer treatment options including radiotherapy, chemotherapy, and surgery, it remains a great challenge globally. Hence, it is important to explore new procedures such as photodynamic therapy (PDT) to improve the therapeutic outcomes and/or modify established protocol with conventional approaches. PDT is a non-invasive treatment with considerable outcomes in cancer therapy. During PDT, photosensitizer (PS) agents absorb a certain wavelength of laser light and produce reactive oxygen species (ROS), which kill cancer cells. PS agent is one of the critical elements besides the tissue oxygen level and physical parameters of the laser to acheive high treatment efficiency in PDT. Berberine (BBR) has potential as a PS but its free form has some limitations such as limited tumor targeting, poor water solubility and systemic toxicity. However, the objective of this study is the co-delivery of berberine (BBR) and citrate gold nanoparticles (AuNPs) on liposomes (Lipo@AuNPs@BBR) as a new PS compound for PDT on A549 lung cancer spheroid cells. Our hypothesis was that AuNPs can have a synergistic effect on BBR in the Lipo@AuNPs@BBR complex, resulting in more photodamage in PDT on A549 cells. Moreover, liposmes provide a platform for the co-delivery of BBR and AuNPs to cells. Hence, the Lipo@AuNPs@BBR complex was synthesized via the thin-film hydration method, and TEM characterization results showed that the size of the Lipo@AuNPs@BBR complex was 100 nm. Moreover, energy-dispersive X-ray spectroscopy (EDS) confirmed that BBR and AuNPs were co-loaded on liposomes while UV-vis spectroscopy showed that the maximum loading was at concentrations of 14 μM (14%) and 11 μg mL⁻¹ (18.33%) for BBR and AuNPs, respectively. Furthermore, the IC₅₀ (80 μg mL⁻¹) concentration of the Lipo@AuNPs@BBR complex combined with a 405 nm laser at 15 J cm⁻² fluency induced cytotoxicity on A549 spheroid cells and resulted in decreasing spheroid cell viability to 34.12%. Finally, the Lipo@AuNPs@BBR complex is not only a potent PS drug in PDT at a safe dose but also considered as a nanotheranositc agent in tumor diagnosis and therapy in vivo studies.