Precise identification of bladder tumors utilizing mucoadhesive thiolated hollow mesoporous silica nanoparticles

• Published in: Journal of controlled release Vol. 380; pp. 1127 - 1140
• Main Authors: Fa, Yu-Chen, Chen, Cheng-Che, Liu, Yi-Chun, Lu, Yu-Huan, Wang, Xin-Hui, Kuo, Yen-Yu, Yang, Chia-Min, Wu, Li-Chen, Ho, Ja-an Annie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.04.2025
• Subjects: Animals; bioadhesives; bladder; Bladder cancer; Cell Line, Tumor; complement; confocal microscopy; cystoscopy; Cystoscopy - methods; dyes; Evans blue; Female; histopathology; Humans; Mice; Mice, Inbred BALB C; mucins; Mucins - metabolism; Mucoadhesiveness; mucosa; Mucous Membrane - metabolism; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Porosity; porous media; Prolonged retention time; silica; Silicon Dioxide - administration & dosage; Silicon Dioxide - chemistry; Sulfhydryl Compounds - chemistry; Thiolated hollow mesoporous silica nanoparticle; Urinary Bladder - metabolism; Urinary Bladder - pathology; urinary bladder neoplasms; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; white light; Evans blue; Prolonged retention time; Thiolated hollow mesoporous silica nanoparticle; Mucoadhesiveness; Bladder cancer
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2025.02.007

Non-muscle invasive bladder cancer (NMIBC) poses significant challenges due to its high recurrence rates and the difficulty in accurately distinguishing tumor lesions. Effective and economical methods for identifying cancerous tissues are urgently needed. In this study, we employed thiolated hollow mesoporous silica nanoparticles loaded with Evans blue (EB@HMSN(E)-SH), a traditional tumor staining dye, in conjunction with white light cystoscopy (WLC) to enhance the detection of bladder tumors. We observed that EB@HMSN(E)-SH exhibited mucoadhesive properties, demonstrating significant aggregation upon interaction with mucin, as assessed by the mucin-particle method using Dynamic Light Scattering (DLS). The permeation-enhancing capability of EB@HMSN(E)-SH was evaluated using tumor spheroid models. Despite repeated flushing, EB@HMSN(E)-SH adhered effectively to the mice bladder mucosa, aiding in the differentiation of tumor tissue from normal and inflammatory lesions, facilitated by the disordered structure of tumor tissue. Tissues stained with EB@HMSN(E)-SH showed co-localization with NBT-2 tumor cells expressing GFP, confirmed by confocal microscopy, which revealed deeper penetration of EB released from HMSN(E)-SH into bladder tumors compared to free EB. The combined use of WLC and EB@HMSN(E)-SH enabled precise identification of tumor-like tissues, corroborated by histopathological examination using H&E staining. The mucoadhesive properties and extended retention time of EB@HMSN(E)-SH complement WLC effectively in identifying NMIBC, suggesting its potential as a promising diagnostic tool. Thiolated hollow mesoporous silica nanoparticles loaded with Evans blue (EB@HMSN(E)-SH) enhanced bladder tumor identification. Combined with white light cystoscopy, EB@HMSN(E)-SH precisely differentiated tumors from normal and inflammatory lesions. [Display omitted] •Thiolated nanoparticles [EB@HMSN(E)-SH] visualize rat bladder tumors.•EB@HMSN(E)-SH boost tumor cell permeation, evident from co-localized EB release.•EB@HMSN(E)-SH targets tumors, sparing healthy/inflamed tissues in vivo for enhanced specificity.•Cystoscopy + EB@HMSN(E)-SH: aids precise tumor removal, advancing surgical interventions.