Remote Manipulation of TRPV1 Signaling by Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for Specific Cancer Therapy.
Shuangling WangYalin WangJie LvChunzhe XuYuxin WeiGuiying WangMeng LiPublished in: Advanced healthcare materials (2024)
Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca 2+ 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 Ca 2+ 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.
Keyphrases
- cancer therapy
- drug delivery
- nitric oxide
- drug release
- neuropathic pain
- photodynamic therapy
- fluorescence imaging
- fluorescent probe
- spinal cord injury
- body mass index
- hydrogen peroxide
- oxide nanoparticles
- nitric oxide synthase
- spinal cord
- cell death
- stem cells
- bone marrow
- risk assessment
- mesenchymal stem cells
- emergency department
- mass spectrometry
- brain injury
- subarachnoid hemorrhage
- cell therapy
- cerebral ischemia