Related Experiment Video
Updated: Jun 17, 2025
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Synergistic intravesical instillation for bladder cancer: CRISPR-Cas13a and fenbendazole combination therapy
Mingkang Liang1,2, Yongqiang Wang3, Lisha Liu1
1Institute of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, 518000, China.
Background:
CRISPR-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.
Methods:
In 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.
Results:
In 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.
Insights
This study introduces a novel CRISPR-Cas13a nanoplatform for bladder cancer, effectively reducing PDL1 expression and enhancing anti-tumor immunity. This innovative approach shows promise for intravesical cancer therapy.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapy
Background:
- CRISPR-Cas13a offers precise RNA editing for cancer therapy.
- Existing CRISPR-Cas13a systems lack intravesical delivery for bladder cancer (BCa).
Purpose of the Study:
- To develop a CRISPR-Cas13a nanoplatform for intravesical instillation in bladder cancer.
- To evaluate the efficacy of inhibiting PDL1 expression and enhancing anti-tumor immunity.
Main Methods:
- A fusion protein CAST (CRISPR-Cas13 and TAT peptide) was assembled with fluorinated chitosan (FCS) nanoparticles (NPs).
- Fenbendazole (FBZ) was encapsulated in BSA and coated with FCS to create FBZ@BSA/FCS NPs for chemo-immunological effects.
- The nanoplatform was administered intravesically in an orthotropic BCa model.
Main Results:
- The CAST-crRNAa/FCS NPs significantly suppressed PDL1 expression in tumor tissues.
- FBZ@BSA/FCS NPs induced tumor cell apoptosis and restructured the immune microenvironment.
- A synergistic effect was observed, enhancing the therapeutic efficacy of intravesical instillation for BCa.
Conclusions:
- A novel RNA editor nanoagent formulation was developed for bladder cancer.
- The study proposes a synergistic therapeutic strategy combining CRISPR-Cas13a and chemo-immunology.
- This approach holds promise for clinical translation of CRISPR-Cas13-based cancer treatments.
