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PPNPs is a multi-layered nanoparticle formulation of paclitaxel developed for the treatment of pancreatic ductal adenocarcinoma (PDAC). The formulation consists of a poly(lactic-co-glycolic acid) (PLGA) core loaded with paclitaxel, stabilized by polyvinyl alcohol (PVA) and Pluronic F127, and surface-coated with poly-L-lysine (PLL). PPNPs are designed to enhance the therapeutic efficacy of paclitaxel by improving its biodistribution and intracellular accumulation while simultaneously targeting the tumor microenvironment. Mechanistically, PPNPs inhibit the Sonic Hedgehog (SHH) signaling pathway and GLI-1 expression, which helps to attenuate tumor desmoplasia and disrupt bidirectional tumor-stromal interactions. Additionally, the formulation promotes the repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive M2 phenotype to a pro-inflammatory M1 phenotype and increases their phagocytic activity. Preclinical studies have demonstrated that PPNPs can sensitize pancreatic cancer cells to gemcitabine and show superior anti-cancer potential compared to free paclitaxel or Abraxane.
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