Research On Ce-based Nanoparticles Loaded With Cisplatin For Tumour Radiotherapy

Objectives:To explore the radiosensitization effect on tumour cells and tumour-bearing mice as well as the basic radiosensitization mechanism of institutionally designed novel nanoscale Li Lu F₄:Ce³⁺scintillators（SCNPs）encapsulating cisplatin（Cis）by the characterization and the stability and toxicity evaluation of the nanoparticles.Materials and Method:First,cisplatin-loaded SCNP nanoparticles（NP+Cis）were synthesized by crystal precipitation,and the materials were characterized by transmission electron microscopy（TEM）,Dynamic light scattering（DLS）,Zeta-potential analyser.In the cell experiments,CCK8 was used to estimate the toxicity of the materials on 4T1 cells,3T3 cells,HUVEC cells,and RAW264.7 cells.Cell colony formation assays,immunofluorescence assays,cell invasion assays,migration tests,cell apoptosis,and cell cycle distribution were used to appraise the radiosensitization effect of the materials.In animal experiments,4T1 tumour-bearing mice were used as a triple-negative breast cancer model and they received a tail vein injection of nanoparticles.The potential risk of toxicity of the materials in the mice was judged through important organ sections and haematological examinations.Then,tumour volume and weight curves of the 4T1 tumour-bearing BALB/c mice were constructed.The effect of radiosensitization in vivo was evaluated by HE and TUNEL staining of tumour sections.Results:Under the electron microscope,the particle was uniform with a clear shell-core structure and the size is 138.6nm.Cytotoxicity experiments showed that SCNPs loaded with cisplatin inhibited 4T1 cells viability.On a larger scale,the SCNPs did not show any obvious toxicity in four types of cells.The SCNPs had higher biosafety than cisplatin.In the in vitro studies,the radiosensitization ratio（SER）of NP+Cis combined with irradiation was 1.69.Moreover,NP+Cis+IR can trigger obvious DNA damage and effectively inhibit cell invasion and migration capability.In contrast to the control group,NP+Cis+IR significantly promoted cell apoptosis and blocked the cell cycle in the G2/M phase.In the in vivo studies,the tumour volume in the NP+Cis+IR group increased more slowly,the tumour weight was smaller,and the body weight of the mice did not change significantly.HE and TUNEL staining of tumour sections also displayed more obvious therapeutic effects.Conclusions:SCNPs containing cisplatin is an emerging nanodrug delivery system（DDS）with high biosecurity and superior radiosensitization functions.