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

[Display omitted] • 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. [ABSTRACT FROM AUTHOR]