In vivo self-assembled bispecific fluorescence probe for early detection of bladder cancer and metastasis

Abstract

Tumor metastasis accounts for over 90% of tumor-related deaths, prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues. However, early detection of metastasis lesions by tracking tumor markers alone has proven to be challenging. Herein, we reported a glycopeptide-based bispecific fluorescence probe (bsProbe) for earlier detection of bladder cancer and metastasis. By simultaneously recognition (tumor & tumor microenvironment) and in vivo self-assembly, the tumor accumulation of bsProbe (12.3% ID/g) was obviously increased by ∼6 fold compared with that in CXCR4 specific fluorescence probe (sProbe), indicating the obvious advantages of bsProbe over existing tumor metastasis detection probes. Additionally, bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio (SNR: approximately 9.5), permitting early diagnosis of lung micro-metastasis (∼1 mm), precise identifying of tumor boundaries and micro-tumors in orthotopic tumor models. More importantly, bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48% and sensitivity of 92.22% in 195 clinical specimens of bladder cancer patients. Taken together, this novel synergetic targeting (CD206 × CXCR4) strategy provides an attractive method for earlier detection of bladder cancer and metastasis, which might be further extended to the imaging-guided surgery of clinical invisible tumors.

Keywords: Bladder cancer; Fluorescence imaging; Nanomaterial; Peptide; Self-assembly.