A synchronized dual drug delivery molecule targeting cancer stem cells in tumor heterogeneity and metastasis

Ji Hyeon Kim, Jung Min Park, Eunsun Jung, Jieun Lee, Jiyou Han, Yoon Jae Kim, Ji Young Kim, Jae Hong Seo, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Cancer stem-like cells (CSCs) represent a key barrier to successful therapy for triple-negative breast cancer (TNBC). CSCs promote the emergence of chemoresistance, triggering relapse and resulting in a poor prognosis. We herein present CDF-TM, a new small molecule-based binary prodrug conjugated with SN-38 and 3,4-difluorobenzylidene curcumin (CDF) that is specifically activated in hypoxic conditions. CDF-TM treatment significantly induced apoptosis in TNBC-derived 3D spheroids, accompanied with caspase-3 activation as well as the attenuation of tumor stemness with evidence of reduction in aldehyde dehydrogenase 1 (ALDH1) activity and the CD44high/CD24low phenotype. An in vivo orthotopic allograft model was used to investigate its effects on tumor growth and metastasis. The dissemination of CSCs from primary allografts was impaired by CDF-TM, along with inhibition of tumor growth via eradication of CSCs and downregulation of multidrug resistance 1 (MDR1). This new small molecule-based binary prodrug offers a novel therapeutic option for metastatic TNBC.

Original languageEnglish
Article number121781
JournalBiomaterials
Volume289
DOIs
Publication statusPublished - 2022 Oct

Bibliographical note

Funding Information:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare , Republic of Korea (grant number: HR20C0021 ), the National Research Foundation of Korea (NRF) (grant number: 2018R1A3B1052702 , 2019M3E5D1A01068998 , 2021R1A2C2009723 , 2019H1A2A1074096 ), and was supported by the Brain Korea (BK) 21 Plus Program .

Funding Information:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR20C0021), the National Research Foundation of Korea (NRF) (grant number: 2018R1A3B1052702, 2019M3E5D1A01068998, 2021R1A2C2009723, 2019H1A2A1074096), and was supported by the Brain Korea (BK) 21 Plus Program.

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

  • Binary prodrug
  • Cancer stem cells
  • MDR1
  • Metastasis
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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