title: Development of a new type of multifunctional fucoidan-based nanoparticles for anticancer drug delivery.
abstract: Fucoidan, a sulfated marine polysaccharide, has many potential biological functions, including anticancer activity. Recently, fucoidan has been reported to target P-selectin expressed on metastatic cancer cells. Increasing research attention has been devoted to the developments of fucoidan-based nanomedicine. However, the application of traditional chitosan/fucoidan nanoparticles in anticancer drug delivery may be limited due to the deprotonation of chitosan at a pH greater than 6.5. In this study, a mutli-stimuli-responsive nanoparticle self-assembled by fucoidan and a cationic polypeptide (protamine) was developed, and their pH-/enzyme-responsive properties were characterized by circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and zeta potential analysis. Enzymatic digestion and acidic intracellular microenvironment (pH 4.5-5.5) in cancer cells triggered the release of an anticancer drug (doxorubicin) from the nanoparticles. The protamine/fucoidan complex nanoparticles with P-selectin mediated endocytosis, charge conversion and stimuli-tunable release properties showed an improved inhibitory effect against a metastatic breast cancer cell line (MDA-MB-231).
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Kun-Ying
authors.initials: KY
authors.lastname: Lu
authors.affiliation: Department of Food Science, College of Life Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan.
authors.forename: Rou
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Department of Biochemistry and Molecular Cell Biology, School of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shen-Chieh
authors.initials: SC
authors.lastname: Chou
authors.affiliation: Department of Food Science, College of Life Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan. Electronic address: tsai5122@gmail.com.
authors.forename: Min-Lang
authors.initials: ML
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Department of Biochemistry and Molecular Cell Biology, School of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: flmi530326@tmu.edu.tw.
authors.forename: Fwu-Long
authors.initials: FL
authors.lastname: Mi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011134:Polysaccharides; D004317:Doxorubicin; C007789:fucoidan
keywords: Drug delivery; Fucoidan; Metastatic cancer cells; Nanoparticles; P-selectin; Polypeptide