A Lysosome-Targeted Near-Infrared Fluorescent Probe with Excellent Water Solubility for Surgery Navigation in Breast Cancer.

To get a tumor-targeted contrast agent for imaging guide resection of tumors, we designed a novel fluorescent probe based on the heptamethine cyanine core, Cy7-MO, which has excellent water solubility and near-infrared photophysical and lysosomal targeting properties. The chemical structure of Cy7-MO was characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The toxicity of Cy7-MO was evaluated by cell counting kit-8. Then, a cellular-level study was conducted to evaluate the suborganelle localization in 4T1-Luc1 cells, and it was also used for surgical navigation in orthotopic breast tumor resection in vivo. The results showed that Cy7-MO was well targeted to lysosomes. Importantly, the Cy7-MO probe was found to be well tolerable and exhibited excellent biocompatibility. Moreover, the orthotopic breast tumor margin was clearly visualized through fluorescence guiding of Cy7-MO. Finally, the correct tumor tissues were completely removed, and a negative margin was obtained successfully, which demonstrated an enhanced precision of surgery.

Chemokine (C-X-C motif) ligand 1/chemokine (C-X-C motif) receptor 2 autocrine loop contributes to cellular proliferation, migration and apoptosis in cervical cancer.

Cervical cancer is the most common malignant tumor in gynecology with high mortality rate, so novel approaches for cervical cancer treatment are urgently needed. In this study, we analyzed the gene expression data and clinicopathological data of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) downloaded from University of California Santa Cruz (UCSC) Xena database. Chemokine (C-X-C motif) ligand 1 (CXCL1) was screened out as a key prognostic gene for cervical cancer. Revealed by the results of ELISA and Western blot, the expression of CXCL1 and chemokine (C-X-C motif) receptor 2 (CXCR2) in cervical cancer cell lines (HeLa and C33A) was significantly higher than that in the primary cervical epithelial cells. Cellular immunofluorescence was used in this study to observe CXCR2 localization. Through CCK8, clone formation assay, wound healing assay and Annexin V/PI staining, it was found that down-regulation of CXCL1 expression or treatment with CXCR2 antagonist (SB 225002) could reduce the cell viability, affect the proliferation, weaken the migration ability, and promote the apoptosis of cervical cancer cells; however, the effect of CXCR2 antagonist was improved after over-expressed CXCL1. CXCL1/CXCR2 chemokine system regulates the proliferation, migration, and apoptosis of cervical cancer cells in the form of an autocrine loop, thus affecting the development of cervical cancer. This study provides a theoretical basis for researching the molecular mechanism of cervical cancer deterioration and development, and brings forward a new idea for the prevention and treatment of cervical cancer.