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Updated: Jun 8, 2025
In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model
Published on: April 12, 2016
Targeted intervention in nerve-cancer crosstalk enhances pancreatic cancer chemotherapy
Jiaqi Qin1, Jingjie Liu1, Zhaohan Wei1
1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Nerve-cancer crosstalk has gained substantial attention owing to its impact on tumour growth, metastasis and therapy resistance. Effective therapeutic strategies targeting tumour-associated nerves within the intricate tumour microenvironment remain a major challenge in pancreatic cancer. Here we develop Escherichia coli Nissle 1917-derived outer membrane vesicles conjugated with nerve-binding peptide NP41, loaded with the tropomyosin receptor kinase (Trk) inhibitor larotrectinib (Lar@NP-OMVs) for tumour-associated nerve targeting. Lar@NP-OMVs achieve efficient nerve intervention to diminish neurite growth by disrupting the neurotrophin/Trk signalling pathway. Moreover, OMV-mediated repolarization of M2-like tumour-associated macrophages to an M1-like phenotype results in nerve injury, further accentuating Lar@NP-OMV-induced nerve intervention to inhibit nerve-triggered proliferation and migration of pancreatic cancer cells and angiogenesis. Leveraging this strategy, Lar@NP-OMVs significantly reduce nerve infiltration and neurite growth promoted by gemcitabine within the tumour microenvironment, leading to augmented chemotherapy efficacy in pancreatic cancer. This study sheds light on a potential avenue for nerve-targeted therapeutic intervention for enhancing pancreatic cancer therapy.
Insights
Researchers developed novel nanoparticles (Lar@NP-OMVs) to target tumor-associated nerves in pancreatic cancer. This approach inhibits nerve growth, enhances chemotherapy, and improves treatment efficacy by disrupting nerve-cancer crosstalk.
Area of Science:
- Oncology
- Nanotechnology
- Cancer Biology
Background:
- Nerve-cancer crosstalk significantly influences tumor progression, metastasis, and therapeutic resistance.
- Targeting tumor-associated nerves in the pancreatic cancer microenvironment presents a therapeutic challenge.
Purpose of the Study:
- To develop a targeted therapeutic strategy for pancreatic cancer by intervening in nerve-cancer signaling.
- To investigate the efficacy of engineered outer membrane vesicles for disrupting tumor-associated nerve function.
Main Methods:
- Engineered outer membrane vesicles (OMVs) from Escherichia coli Nissle 1917, conjugated with nerve-binding peptide NP41 and loaded with larotrectinib (Lar@NP-OMVs).
- Assessed nerve intervention by measuring neurite growth inhibition and disruption of the neurotrophin/Trk signaling pathway.
- Evaluated OMV-mediated repolarization of tumor-associated macrophages and its effect on nerve injury and cancer cell behavior.
- Investigated the impact of Lar@NP-OMVs on gemcitabine-induced nerve infiltration and overall chemotherapy efficacy in pancreatic cancer models.
Main Results:
- Lar@NP-OMVs effectively targeted tumor-associated nerves, inhibiting neurite outgrowth via disruption of the neurotrophin/Trk pathway.
- OMV treatment induced M2-like macrophage repolarization to M1-like phenotype, causing nerve injury and enhancing nerve intervention.
- Lar@NP-OMVs suppressed nerve-triggered proliferation, migration of pancreatic cancer cells, and angiogenesis.
- The strategy significantly reduced gemcitabine-induced nerve infiltration and neurite growth, augmenting chemotherapy efficacy.
Conclusions:
- Engineered OMVs provide a promising platform for nerve-targeted therapy in pancreatic cancer.
- Lar@NP-OMVs demonstrate potential for enhancing pancreatic cancer treatment by modulating the tumor microenvironment and nerve-cancer crosstalk.
- This approach offers a novel therapeutic avenue for overcoming challenges in pancreatic cancer therapy resistance and progression.
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