Preparation and in vitro evaluation of doxorubicin loaded alendronate modified hollow gold nanoparticles for bone-targeted chemo-photothermal therapy

The treatment of malignant bone tumors (including primary bone tumors and metastatic bone tumors) has always been a clinical challenge. The purpose of this study is to design a bone-targeted nano-carrier with photothermal effect to achieve chemo-photothermal therapy (CPT), which allows the minimal use of photothermal agents and chemical drugs to target bone tumors. Alendronate modified hollow gold nanoparticles (HGNPs- ALN) were synthesized using mercapto polyethylene glycol carboxyl (SH-PEG2000-COOH) as the connecting arm, fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) data show that HGNPs-ALN with a particle size of about 80 nm has been successfully synthesized. The hydroxyapatite affinity experiment in vitro indicated that HGNPs-ALN exhibited a high affinity to bone. In addition, the temperature of HGNPs-ALN under near-infrared laser irradiation can rise to 53 °C, which can achieve effective photothermal therapy for bone tumors. Bone-targeted hollow gold nanoparticles (DOX@HGNPs-ALN) loaded with doxorubicin hydrochloride (DOX) were synthesized by one-pot method. By comparing the stability and drug loading of HGNPs-ALN, it was concluded that the optimal mass ratio of HGNPs-ALN (calculated by the amount of gold) to DOX was about 1:2. HGNPs-ALN and DOX@HGNPs-ALN both have good photothermal stability and photothermal transformation properties, and confirmed the safety of HGNPs on human osteosarcoma cells. MTT experiments showed that DOX@HGNPs-ALN had the strongest killing effect on MG-63 osteosarcoma cells under laser irradiation (the killing rate is about 65%). According to these results, it can be considered that DOX@HGNPs-ALN has the potential of CPT synergistic targeting therapy for bone tumors.