Abstract
How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy. In vitro cell experiment shows that human CIK cells labeled with gold nanorods actively target gastric cancer MGC803 cells, inhibit growth of MGC803 cells by inducing cell apoptosis, and kill MGC803 cells under low power density near-infrared (NIR) laser treatment (808-nm continuous wave laser, 1.5 W/cm2, 3 min). In vivo experiment results showed that human CIK cells labeled with gold nanorods could target actively and image subcutaneous gastric cancer vessels via photoacoustic imaging at 4 h post-injection, could enhance immunotherapy efficacy by up-regulating cytokines such as IL-1, IL-12, IL-2, IL-4, IL-17, and IFN-γ, and kill gastric cancer tissues by photothermal therapy via direct injection into tumor site under near-infrared (NIR) laser irradiation. High-performance human CIK cells labeled with Au nanorods are a good novel theranostic platform to exhibit great potential in applications such as tumor-targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy in the near future.
Highlights
Gastric cancer is the fourth commonest cancer and the second leading cause of cancer-related death worldwide [1,2,3]
Our results show that human cytokine-induced killer (CIK) cells loaded with Au nanorods could target gastric cancer in vivo, realized photoacoustic imaging and enhanced immunotherapy, as well as photothermal therapy of gastric cancer, markedly enhanced CIK therapeutic efficacy
Our results provide a new strategy to treat gastric cancer, offer proof-of-principle of practicality of CIK combined with photothermal therapy (PTT) based on human CIK cells loaded with gold nanorods, and exhibit potential clinical applications such as theranostics of gastric cancer and post-operation tumor patients and highly efficient delivery system for gene or drugs in near future
Summary
Gastric cancer is the fourth commonest cancer and the second leading cause of cancer-related death worldwide [1,2,3]. It ranks number two among all malignant tumors. Cellular immunotherapy has become a promising therapeutic method to fight against cancers and is classified as class III medical treatment technology since 2009 in China [6,7,8,9]. Among various cellular immunotherapy methods, lymph cytokine activated killer (LAK) cells were firstly used for anti-cancer therapy by Elizabeth A. Phillips finished a further research of the oncolytic effects executed by LAK cells. A kind of more powerful anti-tumor cell–tumor-infiltrating lymphocytes (TIL) were
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