Gold nanoparticles loaded chitosan encapsulate 6-mercaptopurine as a novel nanocomposite for chemo-photothermal therapy on breast cancer

BACKGROUND: As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect. METHODS: CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay. RESULTS: Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC(50) of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC(50) to 5 and 4.4 µM, respectively. CONCLUSION: The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP. GRAPHICAL ABSTRACT: [Image: see text]