ABSTRACT
Biomaterial-mediated, spatially localized gene delivery is important for the development of cell-populated scaffolds used in tissue engineering. Cells adhering to or penetrating into such a scaffold are to be transfected with a preloaded gene that induces the production of secreted proteins or cell reprogramming. In the present study, we produced silica nanoparticles-associated pDNA and electrospun scaffolds loaded with such nanoparticles, and studied the release of pDNA from scaffolds and cell-to-scaffold interactions in terms of cell viability and pDNA transfection efficacy. The pDNA-coated nanoparticles were characterized with dynamic light scattering and transmission electron microscopy. Particle sizes ranging from 56 to 78 nm were indicative of their potential for cell transfection. The scaffolds were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, stress-loading tests and interaction with HEK293T cells. It was found that the properties of materials and the pDNA released vary, depending on the scaffold's composition. The scaffolds loaded with pDNA-nanoparticles do not have a pronounced cytotoxic effect, and can be recommended for cell transfection. It was found that (pDNA-NPs) + PEI9-loaded scaffold demonstrates good potential for cell transfection. Thus, electrospun scaffolds suitable for the transfection of inhabiting cells are eligible for use in tissue engineering.
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.
ABSTRACT
Materials based on calcium carbonate (CaCO3) are widely used in biomedical research (e.g., as carriers of bioactive substances). The biocompatibility of CaCO3 and dependence of its stability on pH make these materials promising transporters of therapeutic agents to sites with low pH such as a tumor tissue. In this work, we developed an approach to the preparation of nanoscale particles based on CaCO3 (CaNPs) up to 200 nm in size by coprecipitation and analyzed the interaction of the nanoparticles with an anticancer drug: DOXorubicin (DOX). We also showed a prolonged pH-dependent release of DOX from a CaNP nanocarrier and effective inhibition of cancer cell growth by a CaCO3-and-DOX-based composite (CaNP7-DOX) in in vitro models.
