Efficient delivery of fucoxanthin using metal–polyphenol network-coated magnetic mesoporous silica

Abstract

Fucoxanthin (FX) is a natural carotenoid pigment that exhibits antitumor activity and is found primarily in brown seaweed. However, its effectiveness as a therapeutic agent varies owing to low bioavailability, poor water solubility, and poor physicochemical stability. The acidic nature of the tumor microenvironment may be utilized to design and construct a targeted magnetic, acid-labile nano-carrier (FX@Fe₃O₄-mSiO₂-TA) with improved FX bioactivity. A nano-drug delivery system composed of magnetic mesoporous silica coated with a tannic acid–iron network (TA/Fe³⁺) was designed and constructed to improve FX bioactivity based on pH and magnetic targeting in a tumor microenvironment. The external magnetic field guided the carrier to the tumor site.

TA/Fe³⁺ in the outer coating of the carrier was decomposed, resulting in FX release, which was attributed to the low pH of the tumor microenvironment. Drug release was sustained and pH-dependent in vitro, which significantly improved the stability and bioavailability of FX. The simplicity of its preparation and efficacy of the targeted therapeutic suggest the potential of this nano-carrier for application in tumor therapy.

Introduction

Fucoxanthin (FX) is a natural carotenoid pigment that is widely present in various algae, marine phytoplankton, and aquatic shellfish. Its antitumor [1,2], anti-inflammatory [3], and antioxidant [4] properties demonstrate potential benefits for human health. However, FX is hydrophobic and has poor physicochemical stability [[5], [6], [7]], which result in low oral bioavailability and limits its applications in food, cosmetics, and medicine. The stability and bioavailability of FX may be improved by packaging in nanocarriers.

Magnetic mesoporous materials are nanomaterials with broad potential for targeted drug delivery [[8], [9], [10]], biological separation [[11], [12], [13], [14]], and magnetic resonance imaging [15,16]. Fe₃O₄ is considered an ideal magnetic targeting drug carrier because of its biocompatibility and simple production technique [17]. Owing to their richness in pores and easy surface modification, mesoporous silica nanoparticles have garnered considerable interest [18]. Their rich silanol groups can be combined with various molecules to improve the pharmacokinetic and pharmacodynamic properties of drugs. In recent years, some organically-bonded mesoporous silicas have also been reported, such as disulfide-bonded [19] and diselenide-bonded [20], which are more easily degraded in vivo, but such carriers generally have a greater cytotoxicity. An outer layer of mesoporous silica surrounding a magnetically responsive core (Fe₃O₄-mSiO₂) increases the bioavailability, stability, magnetic targeting, and loading rate of the drug [[21], [22], [23]].

Recently, utilizing a green and efficient surface modification method resulted in the formation of a stable metal–polyphenol layer composed of a mesoporous silica surface, natural polyphenols, and metal ion coordination complexes [24]. Tannic acid (TA) is a widely distributed natural plant polyphenol with high biological safety [25,26]. The catechol functional group in the TA structure complexes with iron ions at basic pH to form a ternary complex. This simple packaging process takes a few seconds to complete and does not require other reagents; hence, drug loss can be efficiently prevented [27,28]. The tannic acid–iron network (TA/Fe³⁺) coating layer is pH-responsive and releases the internal drug through cleavage of the metal-ligand coordination bonds in an acidic environment, resulting in the transformation of the ternary complex into a double or single complex, followed by degradation [29,30].

This study aimed to prepare TA/Fe³⁺-encapsulated magnetic mesoporous silica nanoparticles (Fe₃O₄-mSiO₂-TA) for the loading and controlled release of FX. FX@Fe₃O₄-mSiO₂-TA nanoparticles inhibited the growth of human colon cancer cells (HCT116) in vitro and showed weak cytotoxicity against mouse fibroblast cells (L929). The improvement in FX stability and bioavailability and targeted delivery by applying an external magnetic field provides a novel strategy for the construction of FX-responsive anti-tumor vectors with potential for in vivo therapeutic studies.