2. Academic Validation
  3. Potentiating Gilteritinib Efficacy Using Nanocomplexation with a Hyaluronic Acid-Epigallocatechin Gallate Conjugate

Potentiating Gilteritinib Efficacy Using Nanocomplexation with a Hyaluronic Acid-Epigallocatechin Gallate Conjugate

  • Polymers (Basel). 2024 Jan 12;16(2):225. doi: 10.3390/polym16020225.
Ki Hyun Bae 1 2,  Fritz Lai 3,  Qingfeng Chen 3 4,  Motoichi Kurisawa 2 5
Affiliations

Affiliations

  • 1 Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore 138668, Singapore.
  • 2 Institute of Bioengineering and Bioimaging (IBB), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, The Nanos #08-01, Singapore 138669, Singapore.
  • 3 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, The Proteos, Singapore 138673, Singapore.
  • 4 Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  • 5 Graduate School of Advanced Science and Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi 923-1292, Ishikawa, Japan.
PMID: 38257023 DOI: 10.3390/polym16020225
Abstract

Acute myeloid leukemia carrying FMS-like tyrosine kinase receptor-3 (FLT3) mutations is a fatal blood Cancer with a poor prognosis. Although the FLT3 Inhibitor gilteritinib has recently been approved, it still suffers from limited efficacy and relatively high nonresponse rates. In this study, we report the potentiation of gilteritinib efficacy using nanocomplexation with a hyaluronic acid-epigallocatechin gallate conjugate. The self-assembly, colloidal stability, and gilteritinib loading capacity of the nanocomplex were characterized by reversed-phase high-performance liquid chromatography and dynamic light scattering technique. Flow cytometric analysis revealed that the nanocomplex efficiently internalized into FLT3-mutated leukemic cells via specific interactions between the surface-exposed hyaluronic acid and CD44 receptor overexpressed on the cells. Moreover, this nanocomplex was found to induce an eradication of the leukemic cells in a synergistic manner by elevating the levels of Reactive Oxygen Species and Caspase-3/7 activities more effectively than free gilteritinib. This study may provide a useful strategy to design nanomedicines capable of augmenting the therapeutic efficacy of FLT3 inhibitors for effective leukemia therapy.

Keywords

epigallocatechin gallate; gilteritinib; hyaluronic acid; leukemia; nanocomplex.

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