Supramolecular Prodrug Nanovectors for Active Tumor Targeting and Combination Immunotherapy of Colorectal Cancer.
Xianli HuBo HouZhiai XuMadiha SaeedFang SunZhenmei GaoYi LaiTong ZhuFan ZhangWen ZhangHaijun YuPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2020)
Immunotherapy aiming to harness the exquisite power of the immune system has emerged as a crucial part of clinical cancer management. However, only a subset of cancer patients responds to current immunotherapy because of low immunogenicity of the tumor cells and immunosuppressive tumor microenvironment. Herein, host-guest prodrug nanovectors are reported for active tumor targeting and combating immune tolerance in tumors. The prodrug nanovectors are designed by integrating hyaluronic acid (HA) and reduction-labile heterodimer of Pheophorbide A (PPa) and NLG919 into the supramolecular nanocomplexes, where PPa and NLG919 act as a photosensitizer and potent inhibitor of indoleamine 2,3-dioxygenase 1 (IDO-1), respectively. Meanwhile, HA is employed to achieve active tumor targeting by recognizing CD44 overexpressed on the surface of tumor cell membranes. Near infrared (NIR) laser irradiation triggers the release of reactive oxygen species to provoke antitumor immunogenicity and intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Meanwhile, the immunosuppressive tumor microenvironment (ITM) is reversed by NLG919-mediated IDO-1 inhibition. Combination of photodynamic immunotherapy and IDO-1 blockade efficiently eradicates CT26 colorectal tumors in the immunocompetent mice. The host-guest nanoplatform capable of eliciting effective antitumor immunity by inactivating inhibitory immune response can be applied to other immune modulators for improved cancer immunotherapy.
Keyphrases
- cancer therapy
- photodynamic therapy
- hyaluronic acid
- drug delivery
- immune response
- drug release
- reactive oxygen species
- stem cells
- type diabetes
- magnetic resonance
- radiation therapy
- cell therapy
- young adults
- skeletal muscle
- inflammatory response
- high fat diet induced
- positron emission tomography
- insulin resistance
- mass spectrometry
- radiation induced
- squamous cell
- high speed