Nanoscale Coordination Polymer Based on Bacterial Derivatives for Enhanced Radiotherapy in Neuroblastoma

Abstract

Neuroblastoma (NB) is one of the most common extracranial malignancies in children, accounting for 7–8% of childhood malignancies. As one of the main treatments for NB, radiotherapy is limited by various factors in clinics, such as the hypoxia microenvironment in tumor and serious side effects. Herein, we synthesized a kind of nanoscale coordination polymer denoted as Hf@DAP nanoparticles composed of hafnium ion (Hf[Formula: see text] and 2,6-diaminopimelic acid (DAP), one of bacterial derivatives. From the image of transmission electron microscope (TEM), nanoparticles had uniform dispersion. Furthermore, the hydrodynamic diameter measured by dynamic light scattering method was about 190 nm. In this structure, the Hf[Formula: see text] can enhance radiotherapy by effectively enhancing the function of X-ray, and the DAP was a biocompatible ligand for fabricating the nanoscale coordination nanoparticles. Furthermore, Hf@DAP nanoparticles were stable in various mediums and exhibited favorable biocompatibility in various cell lines in vitro. Cell viabilities were tested by cell counting kit (CCK-8) in vitro. There was no obvious cytotoxicity to normal cells, including NIH3T3, RAW264.7, and HUVECs, after incubation with Hf@DAP nanoparticles, indicating biocompatibilities of Hf@DAP nanoparticles. Additionally, a significantly enhanced radiotherapy effect was observed in the N2a cells, a kind of NB cell line, pretreated with Hf@DAP nanoparticles in vitro. The in vivo tumor growth was obviously inhibited in the mice with the combined therapy of Hf@DAP nanoparticles and X-ray, compared with PBS group, Hf@DAP group, and X-ray group. Furthermore, the survival time of the mice in the combined group was significantly prolonged, compared with PBS group. In addition, tissues structures of main organs, such as the lung, liver, spleen, and kidney in these mice, were ordered without the influence of Hf@DAP nanoparticles. Thus, this work proposed a potential radio-sensitizer for further clinical radiotherapy with limited side effects and high efficiency.