Biocompatible snowman-like tumor-targeting dimer nanoparticles for improved delivery efficiency and enhanced anti-tumor therapy

Abstract

• PLA/shellac-FA dimer NPs with tunable shape are designed and prepared to co-load and deliver PTX and CUR . • PTX + CUR-loaded snowman-like PLA/shellac-FA dimer NPs are able to enhance anti-tumor efficacy. • PTX + CUR-loaded snowman-like PLA/shellac-FA dimer NPs activate immune system and reverse immunosuppressive TME . 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. Here, we design and synthesize snowman-like tumor-targeting PLA/shellac-FA dimer nanoparticles (NPs), which demonstrate improved delivery efficiency and enhanced anti-tumor therapy. Paclitaxel (PTX) and curcumin (CUR) are co-loaded in PLA/shellac-FA dimer NPs and their delivery performance is optimized by tuning the particle shape to be snowman-like. In vivo tests confirm that 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 tumor microenvironment (TME). 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.