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

doi:10.1016/j.ijbiomac.2023.126211

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

Int J Biol Macromol. 2023 Oct 1:250:126211. doi: 10.1016/j.ijbiomac.2023.126211. Epub 2023 Aug 9.

Authors

Yu-Wei Yen¹, Yi-Lin Lee¹, Lu-Yi Yu¹, Cheng-En Li¹, Pei-Wei Shueng², Hsin-Cheng Chiu³, Chun-Liang Lo⁴

Affiliations

¹ Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, ROC.
² Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan, ROC; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, ROC.
³ Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu 300, Taiwan, ROC.
⁴ Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, ROC; Medical Device Innovation and Translation Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, ROC. Electronic address: cllo@nycu.edu.tw.

PMID: 37562466
DOI: 10.1016/j.ijbiomac.2023.126211

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.

Keywords: Drug resistance; Fucoidan; Immunogenic cell death; Melatonin; Metastasis; Oral administration; Triple-negative breast cancers.