In recent years, Professor Fan Jinhai’s team from the First Affiliated Hospital (FAH) of Xi’an Jiaotong University (XJTU) has carried out in-depth research on "precise diagnosis and treatment of bladder tumors", developed a series of new technologies for early noninvasive diagnosis and targeted treatment for bladder tumors, and put forward a variety of novel mechanisms for the incidence and development of bladder tumors, making serial progress in the field of precise treatment for bladder tumors.
First, the team constructs the original polypeptide system to realize targeted delivery and margin imaging of bladder tumors.
On September 11, 2024, Professor Fan Jinhai, as the first corresponding author, and PhD Ma Minghai, as the first author, published an online research article entitled "Enhanced Tumor-Targeted Delivery of Argentina-Rich Peptides via a Positive Feedback Loop Orchestrated by Piezo1/integrinβ1 Signaling Axis" in Advanced Science (IF: 14.3). In this study, novel hendeca-arginine peptides are synthesized for targeted delivery in bladder carcinoma, the targeting efficiency is investigated and the mechanism of peptide-based delivery is elucidated. It is demonstrated that the over-activated Piezo1/integrin β1 (ITGB1) signaling axis significantly facilitates tumor-targeted delivery of R11 peptides via macropinocytosis. Furthermore, R11 peptides formed hydrogen bonds with integrin β1, facilitating targeting and penetration into tumor cells. Additionally, R11 peptides protected integrin β1 from lysosome degradation, promoting its recycling from cytoplasm to membrane. Moreover, this findings establish a positive feedback loop wherein R11 peptides activate Piezo1 by increasing membrane fusion, promoting Ca2+ releasing and resulting in enhanced integrin β1-mediated endocytosis in both orthotopic models and clinical tissues, demonstrating effective tumor-targeted delivery. Eventually, the Piezo1/integrin β1 signaling axis promotes cellular uptake and transport of peptides, establishing a positive feedback loop, promoting mechanical delivery to cancer and offering possibilities for drug modification in cancer therapy.
Previously, Professor Fan Jinhai's team constructed a spherical nucleic acid modified by arginine polypeptide and tumor marker Survivin mRNA based on the fluorescence resonance energy transfer (FRET) effect, which reduced the nonspecific signal interference in tumor imaging, and finally realized the efficient and accurate identification of bladder cancer margins in tissues, animals and clinical trials, which contributes to intraoperative imaging and margin identification of bladder cancer, and lays solid foundation for building a new integrated platform for diagnosis and treatment of bladder tumor. Relevant results were published as an article entitled “R11 peptides can promote the molecular imaging of spherical nucleic acids for bladder cancer margin identification” in Nano Research (IF: 9.5).
Second, the team innovatively develops various near-infrared laser technologies to realize photodynamic targeted therapy for bladder tumors. On August 21, 2024, Professor Fan Jinhai, as the first corresponding author, published an online research article entitled "The photothermal effect induces M1 macrophage-derived TNF-α-type exosomes to inhibit bladder tumor growth" in Chemical Engineering Journal (IF: 13.3). In this study, a system that integrates gold-manganese nanomaterials and engineered macrophage-derived exosomes for the synergistic treatment of bladder tumors was developed.
Third, the team establishes a diagnosis and prediction model for patients with bladder cancer, expanding a new field for noninvasive diagnosis of bladder cancer from urine.
Professor Fan Jinhai's team developed a high-performance electronic olfactory system based on chemiresistive sensor array, which can be utilized to diagnose bladder cancer quickly, non-invasively and accurately by smelling clinical urine samples, and finally achieve high accuracy (96.67%), high sensitivity (100%) and high specificity (83.33%) for healthy controls and bladder cancer patients. The artificially intelligent chemiresistive sensor array made of polyaniline film constructed in this study can successfully distinguish urine samples of patients with bladder cancer from those of healthy controls, and can monitor patients with postoperative recurrence, which can be used for large-scale screening, clinical diagnosis and prognosis monitoring, providing novel ideas for early diagnosis and treatment of bladder cancer.
In this study, significant progress has been made in the field of noninvasive diagnosis of bladder cancer from urine, and relevant findings are finally published as a research article entitled "Artificially Intelligent Olfaction for Fast and Noninvasive Diagnosis of Bladder Cancer from Urine" in ACS Sensors (IF: 8.9). Professor Fan Jinhai, Associate Professor Wu Weiwei from intelligent sensing team of Xidian University and Professor Hossam Haick from Israel Institute of Technology are the co-corresponding authors of this article.
This article is selected as the Cover Article of ACS Sensors.
At the same stage, the team developed a ratiometric gold nanosensor based on surface-enhanced Raman scattering (SERS), which can detect bladder tumor markers in urine samples. By normalizing TK1 target signal and GAPDH internal reference signal, the expression level of TK1 mRNA was determined with high sensitivity and specificity, and a single tumor cell was imaged at the Raman level for the first time, which realized the detection of bladder tumor with high sensitivity (80%) and high specificity (100%) in urine samples. By normalizing the target signal and the internal reference signal, non-specific confounding factors in the detection process were effectively eliminated, the expression level of tumor nucleic acid markers in urine was accurately determined, and noninvasive detection of bladder tumor with high sensitivity and specificity was realized through urine samples. These research results were published as an article entitled "Multiplex ratiometric gold nanoprobes based on surface-enhanced Raman scattering enable accurate molecular detection and imaging of bladder cancer" in Nano Research (IF: 9.5).
