Smart Modification on Magnetic Nanoparticles Dramatically Enhances Their Therapeutic Properties

Abstract

Magnetic nanoparticles (MNP) are employed as nanocarriers and in magnetic hyperthermia (MH) for the treatment of cancers. Herein, a smart drug delivery system composed of MNP functionalized with the cytotoxic drug gemcitabine (MNP-GEM) has been thoroughly evaluated. The linker employed is based on a disulfide bond and allows the controlled release of GEM under a highly reducing environment, which is frequently present in the cytoplasm of tumor cells. The stability, MH, and the interaction with plasma proteins of the nanoparticles are evaluated, highlighting their great potential for biological applications. Their cytotoxicity is assessed in three pancreatic cancer cell lines with different sensitivity to GEM, including the generation of reactive oxygen species (ROS), the effects on the cell cycle, and the mechanisms of cell death involved. Remarkably, the proposed nanocarrier is better internalized than unmodified nanoparticles, and it is particularly effective in PANC-1 cells, resistant to GEM, but not in non-tumoral keratinocytes. Additionally, its combination with MH produces a synergistic cytotoxic effect in all cancer cell lines tested. In conclusion, MNP-GEM presents a promising potential for treating pancreatic cancer, due to multiple parameters, such as reduced binding to plasma proteins, increased internalization, and synergistic activity when combined with MH.

New Insights into the Biological Response Triggered by Dextran-Coated Maghemite Nanoparticles in Pancreatic Cancer Cells and Their Potential for Theranostic Applications

“…A cell viability assay revealed that the toxicity of our nanoformulation of DIO-NPs starts with a dose of 42 μg/mL reaching a 50% reduction in cell metabolic activity at a dose of 56 μg/mL (1 mM) of DIO-NPs after 72 h. Different from our results, Lafunete-Gomez et al (2021) [ 46 ] indicated that dextran-coated ɣ-Fe 2 O 3 NPs with a larger size (of around 100 nm) caused no toxicity in PANC-1 cells up to a concentration of 2 mg Fe/mL after 72 h. Another study showed that, without affecting cell viability, dextran-coated ɣ-Fe 2 O 3 NPs of about 75 nm cause oxidative stress and genotoxicity at a dose of 4 μg/mL after 24 h [ 47 ]. In this regard, further research will be necessary to determine an exact time frame for the clearance of DIO-NPs by the reticuloendothelial system (RES) in vivo in order to prove their cytotoxicity on pancreatic cells.…”

A Fast, Reliable Oil-In-Water Microemulsion Procedure for Silica Coating of Ferromagnetic Zn Ferrite Nanoparticles Capable of Inducing Cancer Cell Death In Vitro

“…Moreover, the silica chemistry facilitates the easy attachment of functional molecules-especially those bearing amine of carboxyl groups-thus adding new functionalities to the hybrid nanostructures, such as fluorescence [29][30][31] and therapeutic [31][32][33] and catalytic functions [34]. As it was recently demonstrated, the attachment of a chemotherapeutic agent to the MNPs, reduced the cytotoxic effect of the drug in non-cancerous cells, improved the internalization in cancer cells, and its activity was synergistically enhanced in combination with magnetic hyperthermia [35]. Thus, the controlled encapsulation of the MNPs in a silica shell, by preserving their magnetic properties, enhancing their biocompatibility, and increasing their ability for functionalization with various functional groups represents a huge potential for future clinical translation of the MH technique.…”

Autophagy and the Lysosomal System in Cancer

“…Moreover, nanocarriers can release their therapeutic cargo in a stable and controlled manner. A plethora of stimuli, such as changes in pH, redox, temperature, or magnetic forces, can trigger the release of drugs by evoking a change in the structures of the nanocomplex, to ensure toxicity exclusively into target tissue, without affecting healthy tissues [219].…”