Stimuli-responsive “theranostic” nanocomposite hydrogels based on β-cyclodextrin containing Fe3O4 and Bi2O3 nanoparticles for targeted delivery of methotrexate

Abstract

The present study aimed to design and development of novel “theranostic” hydrogels-based drug delivery system (DDSs) composed of beta-cyclodextrin (β-CD), poly(N,N´-dimethylamino)ethyl methacrylate) (PDMAEMA), and Fe3O4 and Bi2O3 nanoparticles (NPs). Methotrexate (MTX) was loaded into the fabricated hydrogels as an anti-cancer drug. Drug encapsulation efficiencies for S1 and S2 samples were obtained as 77.74 and 81 %, respectively. In vitro drug release study verified pH-dependent and sustained drug release behavior of the formulated S1/MTX and S2/MTX. Cytocompatibilities of the hydrogels were approved using MTT-assay on MCF-7 cells. In contrast, the drug-loaded hydrogels showed time- and concentration-dependence cytotoxicities. As MTT-assay results, IC50 in time period of 48 h for free MTX, S1/MTX, and S2/MTX were quantified as 55, 27 and 27 µgmL−1 based on concentration of MTX. Therefore, S1/MTX and S2/MTX possesses higher anti-cancer activities owing to sustained and “smart” release of drug that could reduce drug dosage and side effects. The presence of Fe3O4 NPs and Bi2O3 NPs in the hydrogels allows diagnosis by MRI and CT, respectively. In addition, Bi2O3 NPs is suggested as efficient X-ray radiosensitizer for increasing the efficiency of radiotherapy. Therefore, the fabricated hydrogels have potential for synergistic chemoradiotherapy and can be exploited in medical imaging.