177Lu-Labeled Near-infrared Upconversion Nanoparticles for targeted theranostics of Breast Cancer Lymphatic Metastases

Abstract The theranostics of lymph node metastasis has always been one of the major obstacles to defeating breast cancer and an important decisive factor in the prognosis of patients. Herein, we design NaGdF4:Yb,Tm@NaLuF4 upconversion nanoparticles with PEG and anti-HER2 monoclonal antibody (trastuzumab, Herceptin) (NP-mAb) conjugation for targeting lymphatic metastasis. Radionuclides 177Lu could be chelated by the bisphosphate groups of NP-mAb. The obtained 177Lu-NP-mAb exhibited excellent radiolabeling stability and show high accumulation and prolong retention in the lymph node metastasis after intratumoral injection into the footpad by SPECT/CT imaging. Utilizing the β rays released by 177Lu, 177Lu-NP-mAb could not only decrease the number of lymph node metastasis, but also significantly improve therapeutic efficiency of lymph node metastasis. Additionally, 177Lu-NP-mAb induce no obvious toxicity to treated mice through blood routine, live and spleen function assay. Therefore, 177Lu-NP-mAb we designed could be acted as excellent theranostics agents for lymph node metastasis, providing a potential alternative treatment option for lymph node metastasis therapy.