pH-Responsible Doxorubicin-Loaded Fe 3 O 4 @CaCO 3 Nanocomposites for Cancer Treatment.
Victoriya PopovaYuliya PoletaevaAlexey S ChubarovElena DmitrienkoPublished in: Pharmaceutics (2023)
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 Fe 3 O 4 @CaCO 3 composites synthesis was proposed. For the procedure, oleic acid-modified Fe 3 O 4 nanoparticles were coated with porous CaCO 3 using an ion coprecipitation technique. PEG-2000, Tween 20, and DMEM cell media was successfully used as a stabilization agent and template for Fe 3 O 4 @CaCO 3 synthesis. Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) data were used for the Fe 3 O 4 @CaCO 3 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 Fe 3 O 4 @CaCO 3 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 Fe 3 O 4 @CaCO 3 /DOX displayed high stability at neutral pH and efficient acid-responsive drug release. The series of DOX-loaded Fe 3 O 4 @CaCO 3 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 Fe 3 O 4 @CaCO 3 nanocomposite is sufficient to inhibit 50% of Hela cells, which shows a high prospect for cancer treatment. The stability experiments for DOX-loaded Fe 3 O 4 @CaCO 3 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 Fe 3 O 4 @CaCO 3 nanoplatform exhibits good performance in the cancer treatment area.
Keyphrases
- drug delivery
- drug release
- cancer therapy
- magnetic resonance
- reduced graphene oxide
- molecularly imprinted
- induced apoptosis
- single cell
- mental health
- squamous cell carcinoma
- photodynamic therapy
- magnetic resonance imaging
- quantum dots
- minimally invasive
- machine learning
- wound healing
- carbon nanotubes
- stem cells
- physical activity
- electron microscopy
- single molecule
- tissue engineering
- cell proliferation
- computed tomography
- drug induced
- emergency department
- mesenchymal stem cells
- monte carlo
- endoplasmic reticulum stress
- atomic force microscopy