RGD peptide/dextran sulfate-based nanocarriers loaded with triptolide for double-targeted apoptosis of both tumor
Yaning Ge1, Xin Zhu1, Zhengxian Zhang1
1School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan Province 450046, PR China.
Abstract:
Triptolide (TP) is a promising anti-tumor candidate derived from the herb Tripterygium wilfordii, but its poor water solubility and multi-organ toxicity limit its application. Here, we developed novel nanoparticles (TP-SP@NPs) modified with dextran sulfate and RGD peptide for double-targeted delivery of TP to both tumor cells and pro-tumor macrophages in pancreatic cancer treatment. TP-SP@NPs exhibited suitable particle size (about 98 nm), good stability and controlled release performance. TP-SP@NPs showed high cellular uptake in Pan02 cells and M2 macrophages through αvβ3 integrin-RGD interaction and SR-A-DS interaction, effectively inhibiting tumor growth by triggering apoptosis of these cells. In Pan02 tumor-bearing mice, TP-SP@NPs specifically accumulated at the tumor site and efficiently decreased the number of M2 macrophages, thereby exerting better curative effect on pancreatic cancer and lower systemic toxicity as compared with TP. As a result, TP-SP@NPs had achieved selective anti-tumor effect, good biosafety and great promise in clinical application.
Insights
Novel nanoparticles effectively deliver triptolide (TP) to pancreatic tumors and suppressive macrophages. This targeted approach enhances anti-cancer effects and reduces toxicity, showing promise for clinical pancreatic cancer treatment.
Area of Science:
- Nanotechnology
- Pharmacology
- Oncology
Background:
- Triptolide (TP) shows anti-tumor potential but faces limitations due to poor water solubility and systemic toxicity.
- Targeted delivery systems are crucial for improving the efficacy and safety of anti-cancer drugs like TP.
Purpose of the Study:
- To develop novel, dual-targeted nanoparticles (TP-SP@NPs) for enhanced delivery of TP to pancreatic cancer cells and tumor-associated macrophages.
- To evaluate the anti-tumor efficacy and biosafety of TP-SP@NPs in preclinical models of pancreatic cancer.
Main Methods:
- TP-SP@NPs were engineered with dextran sulfate (DS) and RGD peptide for specific targeting.
- Nanoparticle characterization included size, stability, and drug release studies.
- Cellular uptake and apoptosis induction were assessed in Pan02 cells and M2 macrophages.
- In vivo studies utilized Pan02 tumor-bearing mice to evaluate tumor accumulation, M2 macrophage reduction, therapeutic efficacy, and systemic toxicity.
Main Results:
- TP-SP@NPs demonstrated optimal particle size (~98 nm), good stability, and controlled release.
- Enhanced cellular uptake was observed in Pan02 cells and M2 macrophages via RGD-integrin and DS-SR-A interactions.
- TP-SP@NPs effectively inhibited tumor growth by inducing apoptosis in target cells.
- In vivo, TP-SP@NPs selectively accumulated in tumors, reduced M2 macrophage populations, and showed superior therapeutic effects with lower toxicity compared to free TP.
Conclusions:
- TP-SP@NPs represent a promising dual-targeted nanodelivery system for pancreatic cancer therapy.
- The developed nanoparticles offer improved anti-tumor efficacy and enhanced biosafety, warranting further clinical investigation.
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