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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Nutrient-delivery and metabolism reactivation therapy for melanoma
Yang Chen1,2, Chaochao Wang1,2, Yelin Wu1
1Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University Cancer Center, School of Life Sciences and Technology, Tongji University, Shanghai, P. R. China.
Abstract:
To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.
Insights
This study introduces a novel nutrient-based strategy to treat melanoma by reactivating metabolic pathways. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) effectively inhibited melanoma cell proliferation and eradicated tumors via photothermal therapy.
Area of Science:
- Oncology
- Metabolic Engineering
- Nanomedicine
Background:
- Tumor cells exhibit altered metabolism to support rapid proliferation.
- While suppressing hyperactivated metabolism inhibits tumor growth, the therapeutic potential of reactivating downregulated metabolic pathways is largely unexplored.
- Melanoma, a significant form of skin cancer, presents unique metabolic challenges.
Purpose of the Study:
- To investigate a nutrient-based metabolic reactivation strategy for effective melanoma treatment.
- To develop L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) for targeted tyrosine supplementation and melanogenesis reactivation in melanoma cells.
- To evaluate the therapeutic efficacy of MTyr-OANPs combined with photothermal therapy.
Main Methods:
- Construction of L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) for targeted delivery of L-tyrosine.
- Reactivation of melanogenesis in melanoma cells using MTyr-OANPs.
- Assessment of melanoma cell proliferation and glycolysis inhibition.
- In vivo studies using B16F10 melanoma-bearing mice treated with MTyr-OANPs and photothermal therapy.
Main Results:
- MTyr-OANPs treatment reactivated melanogenesis, significantly impeding melanoma cell proliferation.
- Melanoma cell proliferation was primarily inhibited through the suppression of glycolysis.
- Melanin, generated via melanogenesis, served as an effective photothermal agent.
- Complete tumor eradication was achieved in B16F10 melanoma-bearing mice through combined MTyr-OANPs and photothermal therapy.
Conclusions:
- Metabolic reactivation, specifically melanogenesis, presents a viable therapeutic strategy for melanoma.
- Targeted nutrient supplementation using nanomicelles can effectively modulate tumor cell metabolism.
- The combination of metabolic reactivation and photothermal therapy offers a potent approach for melanoma treatment.
- This study highlights the potential of specific nutrients as activators of metabolic pathways for cancer therapy.
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