Targeting of CXCR1 on Osteosarcoma Circulating Tumor Cells and Precise Treatment via Cisplatin Nanodelivery

Metastasis and chemotherapy resistance are the key factors affecting the effectiveness of osteosarcoma (OS) treatments. CXCR1 overexpression is found to be closely related to chemotherapy resistance and anoikis resistance in OS cell subtypes with high metastasis potential. Further study demonstrates that CXCR1 is highly expressed on circulating tumor cell (CTC)-derived cells with cancer stem cell characteristics. Then, a CXCR1 targeting peptide is designed and synthesized to competitively inhibit the IL-8/CXCR1 pathway and to improve the cisplatin sensitivity of CTCs. Fluorescence-labeled magnetic nanoparticles (NPs) with pH-responsive cisplatin release are fabricated and linked with the CXCR1 targeting peptide (Cis@MFPPC). Results demonstrate that CTC survival could be inhibited effectively by the targeting nanoparticles in vivo. Cis@MFPPC can also inhibit OS growth and pulmonary metastasis in an orthotopic model and patient-derived tumor xenograft model. This study verifies the clinical significance of CXCR1 as a therapeutic target and provides a drug delivery NP system for precise treatment of OS.