Construction of pH/near-infrared laser stimuli-responsive drug delivery system and its application in treatment of oral squamous cell carcinoma

Min Changqin; Huang Ying

doi:10.12307/2026.607

Abstract：BACKGROUND:Oral squamous cell carcinoma is the most common malignant tumor in the oral and maxillofacial region.Common clinical treatments are difficult to achieve satisfactory results.Therefore,the development of new materials and treatment strategies is of great clinical significance for the treatment of oral squamous cell carcinoma. OBJECTIVE:To construct the pH/near-infrared laser responsive complex by integrating polydopamine and doxorubicin with nanohydroxyapatite as drug carrier,and investigate its photothermal and chemical synergic therapeutic effect and mechanism of the complex on oral squamous cell carcinoma HSC-4 cells. METHODS:Nanohydroxyapatite drug carriers were prepared by hydrothermal method,loaded with photothermal reagent polydopamine and chemotherapeutic drug doxorubicin,and nanohydroxyapatite-polydopamine-doxorubicin complexes were constructed.The morphology,surface charge,ultraviolet-near-infrared spectrum,crystal form and photothermal properties of the complex were characterized.The nanohydroxyapatite-polydopamine-doxorubicin complex was immersed in PBS with different pH values,and 808 nm near-infrared laser irradiation was added in pH=5 PBS to detect the drug release behavior.CCK-8 assay was used to detect the cytotoxic effect of nanohydroxyapatite-polydopamine-doxorubicin complex combined with laser irradiation on human oral tongue squamous cell carcinoma HSC-4 and mouse fibroblast L929.The effect of nanohydroxyapatite-polydopamine-doxorubicin complex combined with laser irradiation on HSC-4 cell apoptosis was detected by flow cytometry.The uptake and distribution of nanohydroxyapatite-polydopamine-doxorubicin complex by HSC-4 cells were detected by flow cytometry and laser confocal microscopy. RESULTS AND CONCLUSION:(1)The nanohydroxyapatite-polydopamine-doxorubicin complex showed a uniform rod-like structure,and the Zeta potential value change and ultraviolet-visible spectrum confirmed that the complex was successfully prepared.The nanohydroxyapatite-polydopamine-doxorubicin complex had good photothermal conversion performance and photothermal stability,and the drug release had an early burst release and a late sustained release behavior,and had pH/near-infrared laser stimulation response performance.Under 808 nm near-infrared light irradiation,the complex had a high-efficiency and low-toxic photothermal-chemical combined treatment effect against oral squamous cell carcinoma,and could promote HSC-4 cell apoptosis.The nanohydroxyapatite-polydopamine-doxorubicin complex could be taken up by HSC-4 cells.With the increase of culture time and laser irradiation,the amount of cell uptake of the complex increased,and doxorubicin was released into the nucleus and kills tumor cells.(2)The results show that the nanohydroxyapatite-polydopamine-doxorubicin complex has good photothermal performance and pH/near-infrared laser stimulation,and exhibits potential photothermal-chemical synergistic anti-tumor effects under 808 nm near-infrared light irradiation.