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Updated: Aug 23, 2025
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Efficient Delivery of P3H4 siRNA and Chlorin e6 by cRGDfK-Installed Polyarginine Nanoparticles for Tumor-Targeting
Lin Hao1, Zhenduo Shi1,2, Yang Dong1,3
1Department of Urology, Xuzhou Central Hospital, Xuzhou 221009, China.
Purpose:
Prolyl 3-hydroxylase family member 4 (P3H4) is a potent prognostic oncogene in bladder cancer (BC), and the inhibition of P3H4 suppresses BC tumor growth. This study aimed to evaluate the efficiency of P3H4 inhibition for BC tumor therapy via tumor-targeting nanoparticles.
Methods And Results:
A linear polyarginine peptide (R9) was synthesized, azide-modified, and then assembled with cyclic pentapeptide cRGDfK. Chlorin e6 (ce6)-conjugated CH3-R9-RGD nanoparticles were prepared for the delivery of siP3H4 into T24 cells in vitro and BC tumors in vivo. Dynamic light scattering analysis identified that the optimum CH3-R9-RGD@siP3H4 molar ratio was 30/1. CH3-R9-RGD@ce6/siP3H4 nanocomposites decreased P3H4 expression and cell proliferation and promoted reactive oxygen species production, apoptosis, and calreticulin exposure in T24 cells in vitro. In vivo experiments showed that CH3-R9-RGD@ce6/siP3H4 nanocomposites caused pathological changes, suppressed BC tumor growth, promoted caspase 3 expression, and enhanced calreticulin exposure in tumor cells.
Conclusions:
The tumor-targeting CH3-R9-RGD nanocomposites encapsulating siP3H4 and ce6 might be an alternative therapeutic strategy or intravesical instillation chemotherapy for BC.
Insights
Targeted nanoparticles effectively delivered siP3H4 to bladder cancer (BC) cells, inhibiting tumor growth and offering a potential new therapy. This approach shows promise for intravesical instillation chemotherapy in BC treatment.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Prolyl 3-hydroxylase family member 4 (P3H4) is a key oncogene in bladder cancer (BC).
- Inhibiting P3H4 can suppress BC tumor progression.
- Novel therapeutic strategies are needed for BC treatment.
Purpose of the Study:
- To evaluate the efficacy of P3H4 inhibition for bladder cancer therapy.
- To develop tumor-targeting nanoparticles for delivering therapeutic agents to BC.
- To assess the potential of nanoparticle-based chemotherapy for BC.
Main Methods:
- Synthesized and modified a linear polyarginine peptide (R9) and assembled it with cRGDfK.
- Prepared chlorin e6 (ce6)-conjugated CH3-R9-RGD nanoparticles for siP3H4 delivery.
- Investigated the effects of CH3-R9-RGD@ce6/siP3H4 nanocomposites in vitro (T24 cells) and in vivo (BC tumors).
Main Results:
- Nanocomposites effectively delivered siP3H4 into T24 cells and BC tumors.
- In vitro, nanocomposites reduced P3H4 expression, cell proliferation, and induced apoptosis and calreticulin exposure.
- In vivo, nanocomposites suppressed tumor growth, increased caspase 3 expression, and enhanced calreticulin exposure.
Conclusions:
- Tumor-targeting CH3-R9-RGD nanocomposites encapsulating siP3H4 and ce6 show therapeutic potential for BC.
- This strategy could serve as an alternative therapeutic approach for bladder cancer.
- Considered as a potential intravesical instillation chemotherapy for BC.
