Abstract
Chemotherapeutic drugs often used as a first-line treatment of pancreatic cancer (PC) exhibit challenges due to resistance development, lack of selectivity, and tumor heterogeneity. Currently, combination chemo-photothermal therapy is known to enhance the therapeutic efficacy of chemotherapeutic drugs in PC. In this study, we develop adherent gold nanoparticles (GNPs) and paclitaxel (PTX)-loaded PLGA microspheres for the treatment of PC. Polydopamine (pD) was used as a linker to adhere GNPs to the surface of PLGA-Ms and characterized using TEM. Short-term cytotoxicity of GNPs-pD-PTX-PLGA-Ms with or without NIR treatment was evaluated using CCK-8 assays. ROS and western blot assay were performed to determine the intensity of ROS following the treatment of GNPs-pD-PTX-PLGA-Ms with or without NIR in Panc-1 cell line. Successful adhesion of GNPs on the microspheres was confirmed by TEM. CCK-8 assay revealed that GNPs-pD-PTX-PLGA-Ms with NIR showed three-fold higher cytotoxicity, compared to the group without NIR. Furthermore, ROS and western blot assay suggest that GNPs-pD-PTX-PLGA-Ms with NIR showed more ROS generation, followed by downregulation of the expression levels of antioxidant enzyme (SOD2 and CATALASE). These results suggest that the GNPs-pD-PTX-PLGA-Ms in combination with NIR irradiation can provide a synergistic chemo-photothermal therapy for the treatment of PC.
Highlights
Pancreatic cancer is the fourth most common cause of death in the US, and an estimated 53,600 cases of pancreatic cancer were reported in 2017 in both sexes (Carrera et al, 2017)
The absence of these characteristic peaks in PTX-Polylactic-co-glycolic acid (PLGA)-Ms suggests that PTX was dispersed either in molecular or amorphous state
The decrease in crystallinity of PTX-PLGA-Ms would facilitate the degradation of polymer matrix thereby causing the sustained release of drug over a period of time
Summary
Pancreatic cancer is the fourth most common cause of death in the US, and an estimated 53,600 cases of pancreatic cancer were reported in 2017 in both sexes (Carrera et al, 2017). The therapeutic efficacy of chemotherapeutic drugs is known to be improved when photothermal therapy (PTT) is used in combination with a strong near-infrared red (NIR) light for conversion of light into heat (Chen et al, 2017). In order to enhance the efficacy of GNPs as photothermal agent by minimizing their toxicity, PLGA microspheres have been used as a delivery platform for the synergistic PTT of pancreatic cancer. Since PLGA microspheres have large surface area and efficient drug loading capacity, a GNPs-adhered polymeric microsphere based smart drug delivery system was developed for the treatment of pancreatic cancer. Various physicochemical characterization and cellular studies were performed to evaluate the synergistic chemo-photothermal effects of GNPs-adhered and paclitaxel-loaded PLGA microspheres
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