A Study of Glutathione-Responsive Dual-Drug-Loaded Nanoparticles in Anti-Osteosarcoma Treatment

Abstract

We connected polyglutamic acid and methotrexate (MTX) through disulfide bonds to prepare glutathione-responsive nanoparticles (MTX NPs) and encapsulated doxorubicin (DOX) to obtain dual drug-loaded NPs (DOX/MTX NPs) (Fig. 1). The appearance of the carbonyl stretching vibration peak at approximately 1640 cm−1 in the results of the infrared spectrum proved the successful synthesis of three kinds of nanoparticles (NPs) with different feeding ratios. The particle sizes of NPs with different feeding ratios were 100–200 nm, and the encapsulation of DOX slightly increased the size, while the surface charge was always negative. The release of MTX at 10 mM glutathione (GSH) was as high as 91.45%, and that of DOX was 89.44%, suggesting that the breakage of disulfide bonds leads to the disintegration of NPs. The results of the cell experiment showed that the encapsulation of DOX effectively increased toxicity and side effects in 143B cells and significantly induced cell apoptosis, and the inhibition of the migration rate increased as the feeding ratio increased. In animal experiments, DOX/MTX NPs significantly induced tumor cell apoptosis and inhibited cell proliferation and tumor growth. The nanoparticles had excellent tumor-targeting properties. Tumor-targeted NPs with the combined action of the two drugs provided a good strategy for the efficient and precise treatment of osteosarcoma.