Study on pH Sensitive Tantalum Oxide Nanomaterials for Tumor Targeted Imaging and Therapy

OBJECTIVE To synthesize pH sensitive tantalum oxide nanoparticles with cetuximab(C225)(TaO_x-C225 NPs) as target molecule for targeted diagnosis and treatment of lung cancer.METHODS C225 was chose as EGFR ligand and connected to the surface of tantalum oxide nanoparticles(TaO_x NPs), which further modified with the photodynamic drug dihydroporphyhene e6 and chemotherapeutic drug doxorubicin hydrochloride through the amino-carboxyl reaction to produce the EGFR-targeted pH sensitive nanometer drug carriers TaO_x-C225 NPs. The morphology and spectra were characterized by transmission electron microscope(TEM) and UV-visible spectroscopy, respectively. Drug release rate of TaO_x-C225 NPs under different pH conditions was tested by HPLC. Subsequently, the targeting and imaging effects of TaOx-C225 NPs were evaluated through the in vitro cell and in vivo imaging experiments using confocal laser microscopy and fluorescence imaging. Finally, the model of subcutaneous tumor was constructed to evaluate the therapeutic effect of the combination of photodynamic therapy of TaOx-C225 NPs with chemotherap. RESULTS The in vitro imaging results showed that TaOx-C225 NPs were specific uptake by HCC827 cells. In vivo imaging, TaOx-C225 NPs also showed specific tumor accumulation with high tumor-to-background contrast on HCC827 subcutaneous tumor with high EGFR expression. Furthermore, the in vivo tumor treatment study revealed that the therapeutic effect of the TaOx-C225 NPs combined xenon lamp group was significantly better than that of other groups. Moreover, the TaOx-C225 NPs showed no significant toxicity to healthy tissues. CONCLUSION Targeted molecular probe technology and fluorescence imaging technology are used to achieve accurate diagnosis of tumors, the combination of photodynamic therapy and chemotherapy can overcome tumor drug resistance to achieve precise killing of lung cancer. The TaO_x-C225 NPs may have certain reference for future cancer diagnosis and treatment.