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Published on: August 30, 2017
Remote Manipulation of TRPV1 Signaling by Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for Specific
Shuangling Wang1,2, Yalin Wang3, Jie Lv1
1College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China.
Abstract:
Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca2+ influx. However, controllable manipulation of TRPV1 signaling for clinical application has remained elusive due to the challenge in finding a mild and effective method of exerting external stimulus without adverse side effects in living systems. Herein, a TRPV1-targeting near-infrared (NIR) triggered nitric oxide (NO)-releasing nanoplatform (HCuS@PDA-TRPV1/BNN6) based on polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) is developed for specific cancer therapy. Upon NIR irradiation, the NO donor BNN6 encapsulated in NIR-responsive nanovehicles can locally generate NO to activate TRPV1 channels and induce Ca2+ influx. This NIR controlled mode enables the nanoplatform to exert its therapeutic effects below the apoptotic threshold temperature (43°C), minimizing the photothermal damage to normal tissue. Integrating this special NO-mediated therapy with HCuS NPs mediated chemodynamic therapy, the designed nanoplatform exhibits a boosted anticancer activity with negligible systematic toxicity. Together, this study provides a promising strategy for site-specific cancer therapy by spatiotemporally controlled activation of surface ion channels, thus offering a solution to an unmet clinical need in cancer treatment.
Insights
This study introduces a novel nanoplatform that uses near-infrared light to activate TRPV1 channels, releasing nitric oxide (NO) for targeted cancer therapy. This approach enhances anti-cancer effects while minimizing damage to healthy tissues.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Transient Receptor Potential Vanilloid member 1 (TRPV1) channels are potential therapeutic targets in cancer due to their role in calcium (Ca2+) influx.
- Controlling TRPV1 activation for clinical cancer treatment is challenging due to the need for mild, effective external stimuli without adverse effects.
Purpose of the Study:
- To develop a novel nanoplatform for site-specific cancer therapy by controllably activating TRPV1 channels.
- To investigate the efficacy of a near-infrared (NIR) triggered nitric oxide (NO)-releasing system for cancer treatment.
Main Methods:
- A nanoplatform (HCuS@PDA-TRPV1/BNN6) was engineered using polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) encapsulating a NO donor (BNN6).
- The nanoplatform was designed for NIR-triggered NO release to activate TRPV1 channels and induce Ca2+ influx specifically in cancer cells.
- Combined chemodynamic therapy (from HCuS NPs) and NO-mediated TRPV1 activation was employed.
Main Results:
- NIR irradiation successfully triggered localized NO release from the nanoplatform.
- The NO release activated TRPV1 channels, leading to Ca2+ influx and cancer cell death.
- The therapy demonstrated significant anti-cancer activity below the thermal ablation threshold (43°C), minimizing damage to normal tissues.
- The combined therapeutic approach showed boosted anticancer efficacy with negligible systemic toxicity.
Conclusions:
- The developed nanoplatform offers a promising strategy for spatiotemporally controlled activation of ion channels for cancer therapy.
- This approach addresses the unmet clinical need for targeted cancer treatments with reduced side effects.
- The study highlights the potential of NO-mediated TRPV1 activation combined with chemodynamic therapy for effective cancer treatment.
