Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia

Yifeng Xia; Jingnan An; Jiaying Li; Wenxing Gu; Yifan Zhang; Songsong Zhao; Cenzhu Zhao; Yang Xu; Bin Li; Zhiyuan Zhong; Fenghua Meng

Bioactive Materials (Mar 2023)

Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia

Yifeng Xia,
Jingnan An,
Jiaying Li,
Wenxing Gu,
Yifan Zhang,
Songsong Zhao,
Cenzhu Zhao,
Yang Xu,
Bin Li,
Zhiyuan Zhong,
Fenghua Meng

Affiliations

Yifeng Xia: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China; College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, PR China
Jingnan An: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, PR China
Jiaying Li: Orthopedic Institute, Soochow University, Suzhou, 215007, PR China
Wenxing Gu: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China
Yifan Zhang: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China
Songsong Zhao: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China
Cenzhu Zhao: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, PR China
Yang Xu: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, PR China; Corresponding author.
Bin Li: Orthopedic Institute, Soochow University, Suzhou, 215007, PR China
Zhiyuan Zhong: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China; College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, PR China; Corresponding author. Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China.
Fenghua Meng: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China; College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, PR China; Corresponding author. Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China.

Journal volume & issue: Vol. 21
pp. 499 – 510

Abstract

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Acute myeloid leukemia (AML) remains a most lethal hematological malignancy, partly because of its slow development of targeted therapies compared with other cancers. PLK1 inhibitor, volasertib (Vol), is among the few molecular targeted drugs granted breakthrough therapy status for AML; however, its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits. Here, we report that transferrin-guided polymersomes (TPs) markedly augment the targetability, potency and safety of Vol to AML. Vol-loaded TPs (TPVol) with 4% transferrin exhibited best cellular uptake, effective down-regulation of p-PLK1, p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells. Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow. The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood, bone marrow, liver and spleen, effectively enhanced mouse survival rate, and impeded bone loss. This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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