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Pharmaceutical Research

, 36:176 | Cite as

A Sialylated-Bortezomib Prodrug Strategy Based on a Highly Expressed Selectin Target for the Treatment of Leukemia or Solid Tumors

  • Mingqi Liu
  • Xueying Tang
  • Junqiang Ding
  • Mengyang Liu
  • Bowen Zhao
  • Yihui Deng
  • Yanzhi SongEmail author
Research Paper

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

sialic acid-mediated selectin targeting strategy may have great potential in the treatment of related tumors.

KEY WORDS

Bortezomib leukemia selectin-targeting sialic acid tumor-targeted 

ABBREVIATIONS

AV-FITC

Annexin V-FITC

BOR

Bortezomib

BOR-MAN

Bortezomib-mannitol

BOR-S

Bortezomib solution

BOR-SA

Bortezomib-sialic acid

CCK8

Cell Counting Kit-8

FBS

Fetal bovine serum

FF

Free FITC

FM

FITC-MAN

FS

FITC-SA

MAN

Mannitol

MO

Monocytes

NE

Neutrophil

PE-CD115

PE-conjugated CD115 antibody

PE-Gr-1

PE-conjugated Ly-6G/Ly-6C antibody

RTI

Relative Tumor-inhibition index

SA

Sialic acid

TEA

Triethylamine

TI

Tumor-inhibition index

TIRV

Tumor volume inhibition rate (volume)

Notes

Compliance with Ethical Standards

Conflict of Interest

There are no conflicts of interest to declare.

Supplementary material

11095_2019_2714_MOESM1_ESM.docx (301 kb)
ESM 1 (DOCX 301 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mingqi Liu
    • 1
  • Xueying Tang
    • 1
  • Junqiang Ding
    • 1
  • Mengyang Liu
    • 1
  • Bowen Zhao
    • 1
  • Yihui Deng
    • 1
  • Yanzhi Song
    • 1
    Email author
  1. 1.College of PharmacyShenyang Pharmaceutical UniversityBenxiChina

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