A Sialylated-Bortezomib Prodrug Strategy Based on a Highly Expressed Selectin Target for the Treatment of Leukemia or Solid Tumors
This study aimed to explore the potential of sialic acid - related selectin targeting strategy in the treatment of leukemia and some solid tumors. We expected it could “actively” bind tumor cells and kill them, reducing non-specific toxicity to normal cells.
BOR-SA prodrug was synthesized by reacting an ortho-dihydroxy group in SA with a boronic acid group in BOR. Two kinds of leukemia cells (RAW264.7 and HL60 cells), one solid sarcoma cell model (S180 cells) and their corresponding normal cells (monocytes (MO), neutrophil (NE) and fibroblast (L929)) were selected for the in vitro cell experiments (cytotoxicity, cellular uptake, cell cycle and apoptosis experiments). The S180 tumor-bearing Kunming mice model was established for anti-tumor pharmacodynamic experiments.
In vitro cell assay results showed that uptake of BOR-SA by HL60 and S180 cells were increased compared with the control group. BOR-SA induced a lower IC50, higher ratio of apoptosis and cell cycle arrest of tumor cells. In vivo anti-S180 tumor pharmacodynamics experiments showed that mice in the BOR-SA group had higher tumor inhibition rate, higher body weight and lower immune organ toxicity compared with the control group.
sialic acid-mediated selectin targeting strategy may have great potential in the treatment of related tumors.
KEY WORDSBortezomib leukemia selectin-targeting sialic acid tumor-targeted
Cell Counting Kit-8
Fetal bovine serum
PE-conjugated CD115 antibody
PE-conjugated Ly-6G/Ly-6C antibody
Relative Tumor-inhibition index
Tumor volume inhibition rate (volume)
Compliance with Ethical Standards
Conflict of Interest
There are no conflicts of interest to declare.
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