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Updated: Jul 11, 2025
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Small-molecule nanoprodrug with high drug loading and EGFR, PI3K/AKT dual-inhibiting properties for bladder cancer
Guoyin Li1,2, Zewen Song3, Yi Ru2
1College of Life Science and Agronomy Zhoukou Normal University Zhoukou Henan China.
Abstract:
Bladder cancer (BCa) is one of the most common malignancies worldwide. Although multiple efforts have been made, the 5-year survival rate of patients with BCa remains unchanged in recent years. Overexpression of the epidermal growth factor receptor (EGFR) is found in ≈74% of BCa tissue specimens; however, current EGFR-based targeted therapies show little benefit for BCa patients, as the EGFR downstream pathways appear to be circumvented by other receptor tyrosine kinases (RTKs). In this study, two natural products are identified, namely triptolide (TPL) and hesperidin (HSP), that target and inhibit the EGFR and its downstream PI3K/AKT pathway in BCa. To synergistically combine triptolide and hesperidin, a succinic acid linker was employed to conjugate them and formed an amphiphilic TPL-HSP EGFR-targeting prodrug (THE), which further self-assembled to generate nanoparticles (THE NPs). These NPs allowed the EGFR-targeted delivery of the triptolide and hesperidin, and simultaneous inhibition of the EGFR and PI3K/AKT both in vitro and in vivo. This study provides a promising EGFR-targeted delivery approach with the dual inhibition of the EGFR and PI3K/AKT, while also exhibiting a high drug loading and low toxicity. Our formulation may be a suitable option to deliver natural products for BCa treatment by EGFR-targeted therapy.
Insights
Natural products triptolide (TPL) and hesperidin (HSP) were combined into nanoparticles (THE NPs) to target epidermal growth factor receptor (EGFR) in bladder cancer (BCa). This dual-action approach effectively inhibited EGFR and its downstream pathway, offering a promising new therapy.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Bladder cancer (BCa) remains a significant global health challenge with stagnant survival rates.
- Epidermal growth factor receptor (EGFR) is overexpressed in most BCa cases, but current therapies are limited due to pathway circumvention by other receptor tyrosine kinases (RTKs).
- Targeting EGFR and its downstream pathways presents a therapeutic opportunity for BCa treatment.
Purpose of the Study:
- To identify natural products that can inhibit EGFR and its downstream PI3K/AKT pathway in bladder cancer.
- To develop a novel nanoparticle-based drug delivery system for synergistic combination therapy.
- To evaluate the efficacy and safety of the developed formulation for targeted BCa treatment.
Main Methods:
- Identification and conjugation of natural products triptolide (TPL) and hesperidin (HSP) using a succinic acid linker to form an amphiphilic prodrug (THE).
- Self-assembly of the THE prodrug into nanoparticles (THE NPs) for targeted delivery.
- In vitro and in vivo assessment of THE NPs for EGFR and PI3K/AKT pathway inhibition in BCa models.
Main Results:
- The developed THE NPs demonstrated successful EGFR-targeted delivery of TPL and HSP.
- Simultaneous inhibition of both EGFR and the PI3K/AKT pathway was achieved both in vitro and in vivo.
- The formulation exhibited high drug loading capacity and low toxicity.
Conclusions:
- The study presents a novel EGFR-targeted nanoparticle delivery system (THE NPs) for bladder cancer treatment.
- This approach enables synergistic dual inhibition of EGFR and the PI3K/AKT pathway using natural products.
- THE NPs offer a promising, low-toxicity therapeutic strategy for BCa, potentially improving treatment outcomes.
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