Activatable Polymer Nanoenzymes for Photodynamic Immunometabolic Cancer Therapy.
Ziling ZengChi ZhangJingchao LiDong CuiYuyan JiangKanyi PuPublished in: Advanced materials (Deerfield Beach, Fla.) (2020)
Tumor immunometabolism contributes substantially to tumor proliferation and immune cell activity, and thus plays a crucial role in the efficacy of cancer immunotherapy. Modulation of immunometabolism to boost cancer immunotherapy is mostly based on small-molecule inhibitors, which often encounter the issues of off-target adverse effects, drug resistance, and unsustainable response. In contrast, enzymatic therapeutics can potentially bypass these limitations but has been less exploited. Herein, an organic polymer nanoenzyme (SPNK) with near-infrared (NIR) photoactivatable immunotherapeutic effects is reported for photodynamic immunometabolic therapy. SPNK is composed of a semiconducting polymer core conjugated with kynureninase (KYNase) via PEGylated singlet oxygen (1 O2 ) cleavable linker. Upon NIR photoirradiation, SPNK generates 1 O2 not only to exert photodynamic effect to induce the immunogenic cell death of cancer, but also to unleash KYNase and trigger its activity to degrade the immunosuppressive kynurenine (Kyn). Such a combinational effect mediated by SPNK promotes the proliferation and infiltration of effector T cells, enhances systemic antitumor T cell immunity, and ultimately permits inhibition of both primary and distant tumors in living mice. Therefore, this study provides a promising photodynamic approach toward remotely controlled enzymatic immunomodulation for improved anticancer therapy.
Keyphrases
- cancer therapy
- small molecule
- drug delivery
- cell death
- photodynamic therapy
- signaling pathway
- fluorescence imaging
- fluorescent probe
- hydrogen peroxide
- drug release
- magnetic resonance
- lymph node
- dendritic cells
- magnetic resonance imaging
- cell proliferation
- papillary thyroid
- stem cells
- high fat diet induced
- bone marrow
- squamous cell
- skeletal muscle
- regulatory t cells
- computed tomography
- insulin resistance
- lymph node metastasis
- childhood cancer
- cell therapy
- cell cycle arrest
- water soluble