R11 peptides can promote the molecular imaging of spherical nucleic acids for bladder cancer margin identification

One of the critical problems in bladder cancer (BC) management is the local recurrence of disease. However, achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition technology. Herein, survivin molecular beacon (MB) and R11 peptide-linked spherical nucleic acids (SNAs) were synthesized as nanoprobes (AuNP-MB@R11) for sensitive detection of BC margins. Physicochemical properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of SNAs. AuNP-MB@R11 had good stability against nuclease activity and high sensitivity and specificity to detect survivin single strand DNA (ssDNA) in vitro. According to cytology, R11 peptides could increase the BC targeting ability and membrane penetrability of SNAs. Notably, R11 peptides significantly promoted the disintegration of lysosomes and the release of SNAs to enhance fluorescence imaging quality. Further RNA sequencing proved that some genes and pathways related to endocytosis and lysosomes were significantly regulated, such as AGPAT5, GPD1L, and GRB2. In orthotopic BC models and a clinical sample from a patient with BC, AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection compared to those achieved by SNAs. R11 peptide-linked SNAs present promising potential to identify BC margin, which may help to improve the R0 resection rate in surgery and improve patients’ quality of life.