TY - JOUR
T1 - A6 peptide-tagged, ultra-small and reduction-sensitive polymersomal vincristine sulfate as a smart and specific treatment for CD44+ acute myeloid leukemia
AU - Gu, Wenxing
AU - Liu, Tianhui
AU - Fan, Daoyang
AU - Zhang, Jubin
AU - Xia, Yifeng
AU - Meng, Fenghua
AU - Xu, Yang
AU - Cornelissen, Jeroen J.L.M.
AU - Liu, Zhongjun
AU - Zhong, Zhiyuan
PY - 2021/1/10
Y1 - 2021/1/10
N2 - 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.
AB - 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.
KW - CD44
KW - Leukemia
KW - Polymersome
KW - Targeted chemotherapy
KW - Targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=85092495440&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2020.10.005
DO - 10.1016/j.jconrel.2020.10.005
M3 - Article
AN - SCOPUS:85092495440
SN - 0168-3659
VL - 329
SP - 706
EP - 716
JO - Journal of controlled release
JF - Journal of controlled release
ER -