Engineering Transferrin-Decorated Pullulan-Based Prodrug Nanoparticles for Redox Responsive Paclitaxel Delivery to Metastatic Lung Cancer Cells

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  • Xing Zhao
  • Haifei Guo
  • Hriday Bera
  • Huiyang Jiang
  • Yang Chen
  • Xiong Guo
  • Xidong Tian
  • Dongmei Cun
  • Yang, Mingshi

Paclitaxel (PTX) remains a cornerstone in the treatment of locally advanced and metastatic lung cancer. To improve its therapeutic indices against lung cancer, novel redox-sensitive pullulan/PTX-based prodrug NPs (PULL-SS-PTX NPs) were accomplished, which were further surface-decorated with transferrin (TF), a cancer cell-targeting ligand, to afford TF-PULL-SS-PTX NPs. These prodrug NPs (drug content, >37% and average size, 134-163 nm) rapidly dismantled their self-assembled architecture upon exposure to simulated reducing conditions, causing a triggered drug release as compared to the control scaffold (PULL-CC-PTX NPs). These scaffolds also evidenced outstanding colloidal stability, cellular uptake efficiency, and discriminating cytotoxicity between the cancer and healthy cells. Intravenously delivered redox-sensitive NPs exhibited improved tumor-suppressing properties as compared to the control nanovesicles (PULL-CC-PTX NPs) in a B16-F10 melanoma lung metastasis mice model. The targeting efficiency and associated augmented anticancer potentials of TF-PULL-SS-PTX NPs relative to TF-free redox-responsive NPs and Taxol intravenous injection were also established on the transferrin receptor (TFR) overexpressed Lewis lung carcinoma (LLC-luc) cell-bearing mice model. Moreover, the TF-functionalized scaffold displayed a reduced systemic toxicity compared to that of Taxol intravenous injection. Overall, the proposed TF-decorated prodrug NPs could be a promising nanomedicine for intracellular PTX delivery against metastatic lung cancer.

Original languageEnglish
JournalACS applied materials & interfaces
Issue number3
Pages (from-to)4441–4457
Publication statusPublished - 2023

ID: 333634819