A novel method for in situ encapsulation of curcumin in magnetite-silica core-shell nanocomposites: A multifunctional platform for controlled drug delivery and magnetic hyperthermia therapy
Graphical abstract
Introduction
In recent years, many researchers have focused on designing effective drug delivery systems to transport chemotherapeutic agents to the tumor sites and improving the therapeutic efficiency of anticancer drugs [1,2]. Unfortunately, the majority of anticancer drugs on the market have poor solubility and low bioavailability, which limits their efficacy in cancer treatment [3]. To date, many kinds of organic carriers including liposomes [4], hydrogels [5], dendrimers [6], and inorganic carriers including graphene [7], gold [8], carbon nanotube [9], and silica [10] have been used to increase the hydrophilicity and biocompatibility of the anticancer drugs. Among the inorganic nanocarriers, mesoporous silica nanoparticles (MSNs) have received growing attention because of their unique physical and chemical properties [11]. MSNs with controllable size and morphology, have high surface area and pore volume for hosting various hydrophilic and hydrophobic drugs [12].
Furthermore, the surface modification of magnetic nanoparticles with silica coating, leads to the preparation of bifunctional nanostructures with great potential application in biomedicine and pharmacy. For instance, it has been shown that the magnetic mesoporous silica nanoparticles (MMSNs) could be utilized as a contrast agent in MRI analysis [[13], [14], [15]]. Also, such nanocomposites have been employed as an ideal platform for simultaneous chemotherapy and hyperthermia therapy to enhance the therapeutic efficacy of traditional chemotherapy [16].
Generally, there are two common methods for preparation of silica-coated magnetic nanoparticles, including “Stober” [17] and “reverse microemulsion” [18] methods. Although many studies attempt to synthetize hybrid nanomaterials, obtaining such nanocomposites with high monodispersity is still challenging [[19], [20], [21]]. Recently, we presented a novel method for fabrication of magnetite mesoporous silica nanoparticles with core-shell structure and controllable size based on the modified reverse microemulsion method [22]. However, the magnetic mesoporous silica nanoparticles, still face many challenges to act as an ideal carrier for drug delivery applications. The most important of these challenges is the limited amount of encapsulated drugs with hydrophobic nature into the pores of these structures. Traditionally, drug loading into the MSNs is carried out using the “post-loading” method, which adds time-consuming and complicated steps to the synthesis process [23]. In the post-loading method, nanocomposites usually are soaked into the organic or aqueous solution containing drug, and consequently, drug molecules diffuse from the bulk solution into the pores of the silica matrix [23]. Unfortunately, the majority of the drug molecules tend to be adsorbed on the external surface of the MSNs instead of the interior space of the silica pores. This phenomenon results in the blockage of the silica pore gates and, subsequently, the decrease in the amount of drug loaded into the matrix. Moreover, after the injection of the MSNs into the bloodstream, the surface adsorbed molecules would be rapidly removed from the exterior surface before receiving to the target site, leading to the uncontrollable release behavior [24].
“In situ loading” technique is an alternative strategy to facilitate the encapsulation of various drugs into the drug carriers in a one-step procedure. For instance, Wan et al. designed a new strategy for in situ drug loading into the MSNs in a one-pot synthesis method based on the evaporation-induced self-assembly method [25]. In another study by He and co-workers, a new in situ drug loading technique was developed to encapsulate water-insoluble drugs into the monodisperse MSNs with interior surfactant micelles [26]. Despite the significant advantages of “in situ drug loading”, to the best of our knowledge, there are no reports for in situ encapsulation of hydrophobic drugs into the magnetic-mesoporous silica nanoparticles with core-shell structure. It could be due to the many difficulties for the accommodation and retention of drugs into the nanocomposite structure during the synthesis process.
In this research, we developed a novel method for the encapsulation of curcumin as a hydrophobic drug during the synthesis of the core-shell magnetite silica nanocomposites, which has not been reported so far. This method is based on a modified reverse microemulsion system, which curcumin-loaded Fe3O4 nanoparticles in the discrete aqueous phase act as a good host for silica formation. Also, the pH-sensitive release behavior of the fabricated nanocomposites was investigated at neutral (pH = 7.4) and slightly acidic media (pH = 5.0). Moreover, the heat generation ability of the fabricated carrier as a heating source in the magnetic hyperthermia application was evaluated. Moreover, the in vitro cytotoxicity of curcumin, encapsulated in magnetite-silica nanocomposites, was compared to free drug against breast cancer MCF-7 cells.
Section snippets
Chemicals and materials
Iron (III) acetylacetonate (99%), cetyltrimethylammonium bromide (CTAB, 97%), dibenzyl ether (98%), oleylamine (technical grade, 70%), oleic acid, cyclohexane (99%), tetraethyl orthosilicate (TEOS, 98%), ethanol (99.9%), and chloroform were prepared from Merck Company. Curcumin, 1-butanol (99%), and urea (99%) were obtained from Sigma Aldrich. All the reagents used without further purification.
Preparation of curcumin-loaded magnetic silica nanocomposites
Oleic acid-stabilized Fe3O4 nanoparticles (OA- Fe3O4 NPs) were synthesized according to the procedure
Results and discussion
In traditional methods, drug loading into the mesoporous silica or magnetic mesoporous silica nanoparticles was carried out using the impregnation of nanoparticles into the drug solution, which is a complicated and time-consuming process. In this work, we presented an effective route for in situ loading of curcumin as a hydrophobic drug model into the magnetite silica nanocomposites.
To this end (as shown in Fig. 1), at first, OA-Fe3O4 NPs were synthesized via thermal decomposition method. At
Conclusions
In summary, a novel procedure was developed for the encapsulation of the curcumin as a hydrophobic anticancer drug, during the synthesis of the core-shell magnetic silica nanocomposites using a reverse microemulsion system. A transparent and stable microemulsion system was prepared by CTAB/1-butanol, cyclohexane, and water as surfactant/co-surfactant, oil phase, and water phase, respectively. The characterization of the obtained SiO2/Cur@Fe3O4 NPs, was carried out by XRD, FTIR, and TEM
Declaration of Competing Interest
None.
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2022, Colloids and Surfaces B: BiointerfacesCitation Excerpt :In this experiment, 8.3 × 109 and 4.9 × 109 Am−1s−1 were used, respectively. For 4.9 × 109 Am−1s−1, 57 W/g SAR could be used for magnetic hyperthermia with a temperature level (ΔT=6 °C) that would be larger than those reported at higher concentrations of magnetic nanoparticles [52]. The toxic effects of the Fe3O4@SiO2@Sec2@FA nanoparticles on the Hela, MDA-MB-231, and human umbilical vein endothelial cells were measured by a CellTiter-Lumi™ Plus assay.