Effect of biocompatible snowman-like tumor-targeting dimer nanoparticles on delivery efficiency and anti-tumor therapy.

e16347 Background: Chemotherapy is indispensable for the systematic treatment of aggressive malignancies, such as pancreatic ductal adenocarcinoma (PDAC), while delivery vehicles are essential for improving delivery efficiency and enhancing anti-tumor therapy. Methods: We design and synthesize tumor-targeting PLA/shellac-FA dimer nanoparticles (NPs). Paclitaxel (PTX) and curcumin (CUR) are co-loaded in PLA/shellac-FA dimer NPs. In vitro, we apply CCK8 assay to investigate the cell uptake of different particle shape. In vivo, different shape of PLA/shellac-FA dimer NPs are injected to mice model with tumor to investigate their delivery performance and anti-tumor effect. Meanwhile, we apply the flow analysis to explore the effect of different shape of PLA/shellac-FA dimer NPs on tumor microenvironment (TME). Results: In vitro tests demonstrate cell uptake performance is optimized by tuning the particle shape to be snowman-like. In vivo tests confirm improved delivery efficiency and enhanced anti-tumor therapy of snowman-like PLA/shellac-FA dimer NPs. Besides, PTX + CUR-loaded snowman-like PLA/shellac-FA dimer NPs could effectively reduce the proportion of tumor-associated macrophages (TAMs) in lymphocytes and reshape the M1/M2 polarization into an anti-tumor type. Meanwhile, the dimer NPs could enhance the infiltration of cytotoxic T lymphocytes (CTLs), thus activating the immune response in the TME. Conclusions: The results suggest that snowman-like PLA/shellac-FA dimer NPs with a sharp shape can effectively improve the delivery efficiency and enhance the anti-tumor therapy, being a promising system for clinical applications.