Journal
CHEMICAL ENGINEERING JOURNAL
Volume 474, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2023.145766
Keywords
Dimer particle; Tumor-targeting; Sustained release; Anti-tumor therapy; Immune activation
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This study designs and synthesizes snowman-like tumor-targeting nanoparticles that improve drug delivery and enhance anti-tumor therapy. In vivo tests demonstrate that these nanoparticles can effectively reduce tumor-associated macrophages and activate immune responses in the tumor microenvironment.
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 macro-phages (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.
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