pH-Responsible Doxorubicin-Loaded Fe3O4@CaCO3 Nanocomposites for Cancer Treatment

Abstract

A magnetic nanocomposite (MNC) is an integrated nanoplatform that combines a set of functions of two types of materials. A successful combination can give rise to a completely new material with unique physical, chemical, and biological properties. The magnetic core of MNC provides the possibility of magnetic resonance or magnetic particle imaging, magnetic field-influenced targeted delivery, hyperthermia, and other outstanding applications. Recently, MNC gained attention for external magnetic field-guided specific delivery to cancer tissue. Further, drug loading enhancement, construction stability, and biocompatibility improvement may lead to high progress in the area. Herein, the novel method for nanoscale Fe3O4@CaCO3 composites synthesis was proposed. For the procedure, oleic acid-modified Fe3O4 nanoparticles were coated with porous CaCO3 using an ion coprecipitation technique. PEG-2000, Tween 20, and DMEM cell media was successfully used as a stabilization agent and template for Fe3O4@CaCO3 synthesis. Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) data were used for the Fe3O4@CaCO3 MNC’s characterization. To improve the nanocomposite properties, the concentration of the magnetic core was varied, yielding optimal size, polydispersity, and aggregation ability. The resulting Fe3O4@CaCO3 had a size of 135 nm with narrow size distributions, which is suitable for biomedical applications. The stability experiment in various pH, cell media, and fetal bovine serum was also evaluated. The material showed low cytotoxicity and high biocompatibility. An excellent anticancer drug doxorubicin (DOX) loading of up to 1900 µg/mg (DOX/MNC) was demonstrated. The Fe3O4@CaCO3/DOX displayed high stability at neutral pH and efficient acid-responsive drug release. The series of DOX-loaded Fe3O4@CaCO3 MNCs indicated effective inhibition of Hela and MCF-7 cell lines, and the IC 50 values were calculated. Moreover, 1.5 μg of the DOX-loaded Fe3O4@CaCO3 nanocomposite is sufficient to inhibit 50% of Hela cells, which shows a high prospect for cancer treatment. The stability experiments for DOX-loaded Fe3O4@CaCO3 in human serum albumin solution indicated the drug release due to the formation of a protein corona. The presented experiment showed the “pitfalls” of DOX-loaded nanocomposites and provided step-by-step guidance on efficient, smart, anticancer nanoconstruction fabrication. Thus, the Fe3O4@CaCO3 nanoplatform exhibits good performance in the cancer treatment area.

Nylon-6-Coated Doxorubicin-Loaded Magnetic Nanoparticles and Nanocapsules for Cancer Treatment

“…To confirm the components of the MNCs and NCs, the FT-IR spectra of the MNP_OA, MNP_OA_Ny, and NC2 were recorded, and the results are presented in Figure 3. The FT-IR spectrum of the MNP_OA provides the characteristic peaks of OA at 2918 cm −1 , 2837 cm −1 (asymmetric and symmetric -CH2 and -CH3 stretch, respectively), 1707 cm −1 (-C=O asymmetric stretch), 1533 cm −1 , 1441 cm −1 (-COO asymmetric and symmetric stretch), 1417 cm −1 (CH3 umbrella), the magnetite MNPs' core peak at 571 cm −1 (Fe-O stretch), and water OH stretching or O-H on the MNPs' surface at 1630 cm −1 and 3375 cm −1 [21,[91][92][93][94][95][96]. cate/3-aminopropyltriethoxysilane (TEOS/APTES) method [84][85][86][87][88][89][90] with a subsequent 2,4,6-trichloro-1,3,5-triazine reaction.…”

“…The use of OA as a capping agent resulted in a partly hydrophobic coating and polar carboxyl groups with a negative charge (see ζpotential, Table 2). It provides a strongly bonded protective monolayer that enhances the colloidal stability, dispersion, and crystallinity of the MNCs [13,21,104]. On the contrary, DOX has a positively charged NH 2 group and fatty aromatic rings.…”

“…Magnetochemistry 2023, 9, 106 2 of 16 However, efficient vehicle design for effective therapeutic drug delivery poses a significant challenge in clinical cancer treatment. Various nanoscale systems based on polymers, gold, calcium carbonate, silica, magnetic materials, biological components, or bioinspared have been proposed as controlled release methods for DOX [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

“…Particles smaller than 15 nm are removed from the blood through the kidneys, while those higher than 150 nm are absorbed by the liver and spleen and pose problems with vascular structures' penetration and cellular internalization. By combining nanotechnology and responsive DOX delivery systems, various nanocomposites can be synthesized, thus avoiding drug resistance problems [8,13,16,21].…”

“…Controlled drug release in a cancer tissue environment by a pH-stimuli-response is a well-known method with high prospects in this field [8,13,16,21]. pH-responsive constructions should have extremely low drug release properties in plasma (pH~7.4) and healthy tissue.…”