MP18-17: Arginine-rich peptide conjugates enhance tumor-targeted imaging and delivery mediated by the Piezo1/ Integrin β1 axis in bladder cancer
Friday, May 3, 2024 3:30 PM to 5:30 PM · 2 hr. (US/Central)
302B
Abstract
Information
Full Abstract and Figures
Author Block
Jinhai Fan, Minghai Ma*, Xi'an, China
Introduction
Various peptide-based nanoparticles are being developed as a potential treatment for bladder cancer (BC). However, most drugs still cannot penetrate through the dense mucosal barrier due to the urine flush and versatile pressure in the bladder. In order to enhance the penetrating efficiency and drug enrichment and retention, we synthesized a series of arginine-rich peptide conjugates(APC) to realize tumor-targeted imaging and therapy for BC and investigated the mechanism of peptide-targeted delivery.
Methods
Fluorescence in situ hybridization was used to observe the location of peptides. RNA-Seq and bioinformatics were used to explore related proteins. Molecular docking and software analysis were used to predict the binding motif of peptides. Flow cytometry was used to analyze the uptake and the release of Ca2+. Gene transfection, Western Blotting, and qPCR were used to explore gene function. Transmission electron microscope was used to analyze the morphology and distribution of the membrane. Orthotopic BC models and clinical tissues were used to verify the imaging efficiency.
Results
APC could identify the BC margin and distinguish between tumor and normal areas accurately. The mechanical signaling Piezo1/Integrin ß1 axis was involved in the tumor-targeted delivery of APC, which was anchored in the membrane and over-activated in BC. APC could bind with Intergrin ß1 through hydrogen bonds tightly and penetrate tumor cells, then protect Intergrin ß1 from degradation by lysosome through the micropinocytosis pathway. APC could also promote Integrin ß1 to recycle from cytoplasm to membrane, achieving positive feedback delivery. Besides, APC stimulated dynamic morphological alterations and increased membrane curvature, promoting Piezo1 to mediate the release of Ca2+ and enhancing Integrin ß1-mediated endocytosis. APC could target the Piezo1/Integrin ß1 axis in both orthotopic models and clinical tissues of BC, exhibiting satisfactory tumor-targeted imaging and delivery efficiency.
Conclusions
APC can promote the mechanical sense and cellular uptake mediated by the Piezo1/Integrin ß1 axis, which promotes positive feedback delivery, ultimately enhancing tumor-targeted imaging and delivery and realizing the integration of diagnosis and treatment in BC.
Source Of Funding
This work was supported by Natural Science Foundation of China (81901838),Key research and development plan of Shaanxi province (2020SF-195), Key research and development plan of Shaanxi Province(2020SF-123).
Author Block
Jinhai Fan, Minghai Ma*, Xi'an, China
Introduction
Various peptide-based nanoparticles are being developed as a potential treatment for bladder cancer (BC). However, most drugs still cannot penetrate through the dense mucosal barrier due to the urine flush and versatile pressure in the bladder. In order to enhance the penetrating efficiency and drug enrichment and retention, we synthesized a series of arginine-rich peptide conjugates(APC) to realize tumor-targeted imaging and therapy for BC and investigated the mechanism of peptide-targeted delivery.
Methods
Fluorescence in situ hybridization was used to observe the location of peptides. RNA-Seq and bioinformatics were used to explore related proteins. Molecular docking and software analysis were used to predict the binding motif of peptides. Flow cytometry was used to analyze the uptake and the release of Ca2+. Gene transfection, Western Blotting, and qPCR were used to explore gene function. Transmission electron microscope was used to analyze the morphology and distribution of the membrane. Orthotopic BC models and clinical tissues were used to verify the imaging efficiency.
Results
APC could identify the BC margin and distinguish between tumor and normal areas accurately. The mechanical signaling Piezo1/Integrin ß1 axis was involved in the tumor-targeted delivery of APC, which was anchored in the membrane and over-activated in BC. APC could bind with Intergrin ß1 through hydrogen bonds tightly and penetrate tumor cells, then protect Intergrin ß1 from degradation by lysosome through the micropinocytosis pathway. APC could also promote Integrin ß1 to recycle from cytoplasm to membrane, achieving positive feedback delivery. Besides, APC stimulated dynamic morphological alterations and increased membrane curvature, promoting Piezo1 to mediate the release of Ca2+ and enhancing Integrin ß1-mediated endocytosis. APC could target the Piezo1/Integrin ß1 axis in both orthotopic models and clinical tissues of BC, exhibiting satisfactory tumor-targeted imaging and delivery efficiency.
Conclusions
APC can promote the mechanical sense and cellular uptake mediated by the Piezo1/Integrin ß1 axis, which promotes positive feedback delivery, ultimately enhancing tumor-targeted imaging and delivery and realizing the integration of diagnosis and treatment in BC.
Source Of Funding
This work was supported by Natural Science Foundation of China (81901838),Key research and development plan of Shaanxi province (2020SF-195), Key research and development plan of Shaanxi Province(2020SF-123).
Sessions
MP18: Imaging/Uroradiology I
302B