Optimization of cytotoxic properties of magnetic nanoparticle-based doxorubicin delivery system

Doxorubicin (DOX) is a widely used cytotoxic drug with high antitumor activity, but its use is accompanied by side effects. The development of DOX delivery systems that can minimize systemic toxicity and increase therapeutic efficacy is an urgent task in modern oncology. We investigated the process of loading nanoparticles (NPs) with DOX under conditions that promote DOX precipitation in order to achieve maximum sorption efficiency. For this purpose, polymer-stabilized magnetic NPs were synthesized, and the efficiency of loading and precipitation was studied in dependence on the buffer, DOX concentration, and incubation time with the drug. It was shown that in solutions with the most pronounced DOX precipitate formation (phosphate and borate buffers) loading proceeded maximally efficiently. In a phosphate buffer at an initial DOX concentration of 667 μg/mL, the loade was 886 mg DOX/g NPs. The sorption of DOX on NPs under these conditions reached 85% of DOX already within the first hour, and increased to 90% within 3 h. The release of DOX from NPs was 25% at pH 7.4 and 96% at pH 5.4. The survival analysis of EMT-HER2 breast cancer cells showed that the cytotoxicity of NPs loaded with DOX under precipitation conditions was 8 times higher than that of NPs loaded at a concentration of 20 μg/mL, i.e. when DOX does not form a precipitate. This allows us to consider NPs loaded with precipitated DOC as an effective delivery system that, without impairing the cytotoxic properties of the drug, can significantly increase its content and release in tumor cells.