A6 peptide-tagged, ultra-small and reduction-sensitive polymersomal vincristine sulfate as a smart and specific treatment for CD44+ acute myeloid leukemia

Wenxing Gu, Tianhui Liu, Daoyang Fan, Jubin Zhang, Yifeng Xia, Fenghua Meng*, Yang Xu, Jeroen J.L.M. Cornelissen, Zhongjun Liu, Zhiyuan Zhong

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Acute myeloid leukemia (AML) is a severe blood malignancy associated with a high relapse rate. The current clinical chemotherapy is typically perplexed with serious side effects. Here, A6 peptide-tagged, small and reduction-sensitive polymersomal vincristine sulfate (A6-cPS-VCR) is reported as a novel, smart and specific treatment for CD44 positive AML. A6-cPS-VCR stably loaded with 3.3 wt% VCR displays a size of ≈ 31 nm and pronounced selectivity toward CD44-overexpressed MV4-11 leukemia cells. Intriguingly, A6-cPS-VCR effectively represses the outgrowth of orthotopic MV4-11 AML in vivo, as revealed by significant reduction of leukemia burdens in the circulation, bone marrow, liver and spleen, and significantly extends the median survival time of MV4-11 AML-bearing mice. In addition to active targetability and therapeutic benefits, A6-cPS-VCR has the advantage of easy fabrication, rendering it potentially interesting for clinical translation.

Original languageEnglish
Pages (from-to)706-716
Number of pages11
JournalJournal of controlled release
Volume329
Early online date5 Oct 2020
DOIs
Publication statusPublished - 10 Jan 2021

Keywords

  • CD44
  • Leukemia
  • Polymersome
  • Targeted chemotherapy
  • Targeted delivery

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