Fucoidan/chitosan layered PLGA nanoparticles with melatonin loading for inducing intestinal absorption and addressing triple-negative breast cancer progression

Yu Wei Yen, Yi Lin Lee, Lu Yi Yu, Cheng En Li, Pei Wei Shueng, Hsin Cheng Chiu, Chun Liang Lo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Melatonin and fucoidan are naturally active compounds that have been reported to have therapeutic benefits for patients receiving cancer treatment. However, both compounds face significant challenges, including physical, chemical, and biological metabolisms in the gastrointestinal tract, which limit their ability to achieve therapeutic concentrations at the tumor site. Furthermore, the effectiveness of melatonin and fucoidan as adjuvants in vivo is influenced by the route of administration through the digestive system and their accumulation at the endpoint of the tumor. In this study, we developed an oral administration of nanoparticle, MNPs@C@F, that consisted of PLGA nanoparticles modified with chitosan, to promote intestinal microfold cell transcytosis for the delivery of melatonin and fucoidan into tumors. The experimental results indicated that melatonin and fucoidan in the tumors could regulate the tumor microenvironment by decreasing P-gp, Twist, HIF-1α, and anti-inflammatory immune cell expression, and increasing cytotoxic T cell populations following doxorubicin treatment. This resulted in an increase in chemo-drug sensitivity, inhibition of distant organ metastasis, and promotion of immunogenic cell death. This study demonstrates a favorable co-delivery system of melatonin and fucoidan to directly reduce drug resistance and metastasis in TNBC.

Original languageEnglish
Article number126211
JournalInternational Journal of Biological Macromolecules
Volume250
DOIs
StatePublished - 1 Oct 2023

Keywords

  • Drug resistance
  • Fucoidan
  • Immunogenic cell death
  • Melatonin
  • Metastasis
  • Oral administration
  • Triple-negative breast cancers

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