Current advances in the application of nanomedicine in bladder cancer.

Mechanisms and strategies to enhance penetration during intravesical drug therapy for bladder cancer.

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Recent Progress in Nanomaterial-Based Biosensors and Theranostic Nanomedicine for Bladder Cancer

Missed or residual tumor burden results in high risk for bladder cancer relapse. However, existing fluorescent probes cannot meet the clinical needs because of inevitable photobleaching properties. Performance could be improved by maintaining intensive and sustained fluorescence signals via resistance to intraoperative saline flushing and intrinsic fluorescent decay, providing surgeons with sufficiently clear and high-contrast surgical fields, avoiding residual tumors or missed diagnosis. This study designs and synthesizes a photostable cascade-activatable peptide, a target reaction-induced aggregation peptide (TRAP) system, which can construct polypeptide-based nanofibers in situ on the cell membrane to achieve long-term and stable imaging of bladder cancer. The probe has two parts: a target peptide (TP) targets CD44v6 to recognize bladder cancer cells, and a reaction-induced aggregation peptide (RAP) was introduced and effectively reacted with TP via a click reaction to enhance the hydrophobicity of the whole molecule, assembling into nanofibers and further nanonetworks. Accordingly, probe retention on the cell membrane was prolonged, and photostability was significantly improved. Finally, the TRAP system is successfully employed in the high-performance identification of human bladder cancer in ex vivo bladder tumor tissues. This cascade-activatable peptide molecular probe based on the TRAP system enables efficient and stable imaging of bladder cancer. This article is protected by copyright. All rights reserved.

Photostable Cascade Activatable Peptide Self-assembly on a Cancer Cell Membrane for High-Performance Identification of Human Bladder Cancer.

Recently, surface-enhanced Raman scattering (SERS) has been successfully used in the non-invasive detection of bladder tumor (BCa). The internal standard method was considered as an effective ratiometric strategy for calibrating signal fluctuation originated from the interference of measurement conditions and samples. However, it is still difficult to detect the target mRNA quantitatively using the current ratiometric SERS nanosensors. In this study, we developed an internal reference based ratiometric SERS assay. Two kinds of molecular beacons (MB) carrying Raman reporter molecules were anchored on sea-urchin-like Au nanoclusters (AuNCs). Thymidine kinase1 (TK1) MBs with hexachlorofluorescein (HEX) were used to capture tumor biomarker TK1 mRNA, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) MBs with 5(6)-carboxyfluorescein (FAM) were used to offer internal standard signals. The internal reference GAPDH MB can reflect the consistent content of the GAPDH mRNA in single cells. The ratiometric method (I745/I645) can more accurately reflect the content of target mRNA in single cells. The ratiometric nanoprobes had excellent stability (coefficient of variation: 0.3%), high sensitivity (detection limit: 3.4 pM), high specificity (capable of single-base mismatch recognition) and ribozyme-resistant stability. Notably, the nanoprobes can effectively distinguish BCa cells from normal cells, and it was easy to contour the single BCa cell using the ratiometric method. By combining asymmetric polymerase chain reaction (PCR) and ratiometric nanoprobes, it was easy to distinguish the SERS ratio (I745/I645) as low concentration as 10−14 M. Further clinical detection in urine samples from patients with BCa confirmed its potential for early noninvasive diagnosis of BCa with the sensitivity of 80% and specificity of 100%, which is superior to the current urine cytological method.

Multiplex ratiometric gold nanoprobes based on surface-enhanced Raman scattering enable accurate molecular detection and imaging of bladder cancer

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.

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 local recurrence of disease. However, achieving 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 peptides-linked spherical mucleic acids (SNAs) were synthesized as a nanoprobe (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. The AuNP-MB@R11 had good stability against nuclease, high sensitivity and specificity to detect survivin ssDNA in vitro experiment. In cytology, R11 peptides could increase BC targeting ability and membrane penetrability of SNAs. Notably, R11 peptides can significantly promote the disintegration of lysosome and release of SNAs to enhance the fluorescence imaging quality. The further RNA sequencing proved that some genes related with endocytosis and lysosome regulated significantly, such as AGPAT5, GPD1L, TREX1 and APEX1. In orthotopic BC models and a clinical sample from patient with BC, AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection effects compared to those achieved by SNAs. Thus, R11 peptides-linked SNAs presented a promising potential to identify the BC margin, which may help to improve the R0 resection rate in surgery and improve patient’s quality of life.

R11 Peptides Can Promote the Molecular Imaging of Spherical Nucleic Acids for the Bladder Cancer Margin Identification

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

R11 Peptides Can Promote the Molecular Imaging of Spherical Nucleic Acids for the Bladder Cancer Margin Identification