ArticleJournal of experimental & clinical cancer research : CR2024
Synergistic intravesical instillation for bladder cancer: CRISPR-Cas13a and fenbendazole combination therapy.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Beyond DNA editing: how Cas13 redefined programmable RNA manipulation and what still limits its therapeutic promise.Nucleic acids research · 2026Review
- Ferroptosis Induction by Fenbendazole Combined With Photothermal Therapy Triggers Dual-Immunotherapy Against Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- "Ferroptosis-immune" cycle: Research progress of tumor microenvironment responsive nanomaterials in the treatment of pancreatic cancer.iScience · 2026Review
- RNA Regulatory Networks: Key Hubs in the Panorama of Cancer and Emerging Therapeutic Targets.MedComm · 2026Review
- RNA editing: an emerging frontier in cancer therapy - explorations, opportunities, and challenges.International journal of surgery (London, England) · 2026Article
- Application and challenges of smart responsive multifunctional nanoplatforms in integrated diagnosis and treatment of bladder cancer and overcoming therapeutic resistance.Frontiers in oncology · 2026Review
- Current updates on the structural and functional aspects of the CRISPR/Cas13 system for RNA targeting and editing: A next‑generation tool for cancer management (Review).International journal of oncology · 2025Review
- Development of Novel Intravesical Formulation for Bladder Retention Targeting Bladder Disorders.Current drug targets · 2025Review
- Article
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Authors and funding
10 authors.
Funding
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Abstract
backgroundCRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functions in vitro efficiently and specifically, the development of CRISPR-Cas13a-based therapeutic agents for intravesical instillation in bladder cancer (BCa) remains unexplored.
methodsIn this study, we introduce a CRISPR-Cas13a nanoplatform, which effectively inhibits PDL1 expression following intravesical instillation. This system utilizes a fusion protein CAST, created through the genetic fusion of CRISPR-Cas13 and the transmembrane peptide TAT. CAST acts as a potent transmembrane RNA editor and is assembled with the transepithelial delivery carrier fluorinated chitosan (FCS). Upon intravesical administration into the bladder, the CAST-crRNAa/FCS nanoparticles (NPs) exhibit remarkable transepithelial capabilities, significantly suppressing PDL1 expression in tumor tissues.To augment immune activation within the tumor microenvironment, we integrated a fenbendazole (FBZ) intravesical system (FBZ@BSA/FCS NPs). This system is formulated through BSA encapsulation followed by FCS coating, positioning FBZ as a powerful chemo-immunological agent.
resultsIn an orthotropic BCa model, the FBZ@BSA/FCS NPs demonstrated pronounced tumor cell apoptosis, synergistically reduced PDL1 expression, and restructured the immune microenvironment. This culminated in an enhanced synergistic intravesical instillation approach for BCa. Consequently, our study unveils a novel RNA editor nanoagent formulation and proposes a potential synergistic therapeutic strategy. This approach significantly bolsters therapeutic efficacy, holding promise for the clinical translation of CRISPR-Cas13-based cancer perfusion treatments.
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