Hybrid photoactive nanomaterial composed of gold nanoparticles, pheophorbide-A and hyaluronic acid as a targeted bimodal phototherapy

摘要

Modern cancer research is largely focused on the design and development of multifunctional nanomaterials for cancer therapy and diagnosis. In this study, we fabricated a theranostic nanomaterial known as a photomedicine that combines a photothermal therapy (PTT), gold nanoparticles (AuNPs), a photodynamic therapy (PDT), pheophorbide-A (PheoA), and a cancer-targeting agent, hyaluronic acid (HA); this photomedicine also acts as a bimodal phototherapy. The combination of AuNPs and PheoA exerts a synergistic effect on PTT and PDT when irradiated by a laser source with a specific excitation wavelength. When excited by an external laser source, the hybrid nanomedicine generates singlet oxygen from PheoA while simultaneously generating heat from the AuNP, thus demonstrating a higher efficacy than any of the individual agents. The presence of HA on the outer surface of the Au accelerates the cellular uptake of the nanomedicine through CD44 receptors and prevents nonspecific accumulation of the drug in non-cancerous cells. The multifunctional nanoparticles have a diameter of similar to 70 nm and show constant stability in different conditions for up to a week of observation. In vitro and in vivo studies have demonstrated that multifunctional nanomaterials selectively target cells overexpressing CD44 receptor. In vitro photo-activity assays in the lung cancer cell line (A549) show that over 95% of the cells were dead upon laser irradiation. In brief, this newly developed nanomaterial rapidly accumulates in the tumor within 3 h of IV administration and inhibits tumor growth by 95% upon laser irradiation compared with a saline-treated tumor model observed for 24 days.