Nanostructured lipid carrier delivering chlorins e6 as in situ dendritic cell vaccine for immunotherapy of gastric cance
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The recent scientific progress has shown the promising effect of the vaccine in immunotherapy of cancer, which relies on the antigen processing/presentation capability of dendritic cells (DCs). As a result, cancer vaccines targeting DC, which also named as DC vaccine, was a hot-spot in vaccine development. Herein, a nanostructured lipid carrier (NLC) was employed to load chlorin e6 (Ce6) to serve as a potential in situ DC vaccine (NLC/Ce6) for effective immunotherapy of gastric cancer. Taking advantage of the photodynamic effect of Ce6 to generate reactive oxygen species (ROS) under laser irradiation, the NLC/Ce6 was able to trigger cell death and expose tumor-associated antigen (TAA). Moreover, mimicking the natural inflammatory response, the ROS can also recruit the DC for the effective processing/presentation of the in situ exposed TAA. As expected, we observed strong capability DC vaccination efficacy of this platform to effectively inhibit the growth of both primary and distant gastric tumors.
Introduction Cancer immunotherapy is becoming one of the most promising means in cancer management. In particular, the dendritic cells (DCs)-based cancer vaccine showed irreplaceable advantages over other counterparts, including low cost and high safety [1, 2]. As a result, the DC vaccine is becoming a hot-spot of in cancer therapy [3, 4]. Considering the critical role of DCs in the activation of immune responses, the effective antigen processing/presentation of DC is the major obstacle in the development of the DC vaccine [5]. Nonetheless, current DC vaccines usually require complicated processing of related products and the reproducibility is poor and the cost is relatively high [6]. As a result, finding an easy and repeatable approach to trigger effective DC activation for the immune response might be challenging, but is the future of the DC vaccine [7]. The introduction of nanotechnology is a great leap for the advance of vaccine development [8, 9, 10, 11]. However, previous reported nanotechnology-based vaccines usually require repeated injections and relatively high doses to afford the barely feasible immune response [12, 13, 14]. Therefore, the development of a formulation capable of inducing a strong immune
response with reduced dosage is greatly needed. Nanostructured lipid carrier (NLC) as one of the most wellrecognized carriers in drug delivery has shown many virtues over other counterparts, including decent drug loading, preferable biocompatibility, as well as easy fabrication. As a result, many NLC-based drug delivery systems (DDSs) have been proposed for cancer therapy with satisfying performance [15, 16]. Using the enhanced permeability and retention (EPR) effect in tumor sites and the overexpressed antigens on the cancer cell surface, the tumor-targeted drug delivery is becoming more and more assessable [16, 17]. However, the NLC-based vaccines for cancer immunotherapy have rarely been explored, which might be an interesting topic. Photodynamic therapy (PDT) has been shown by many previous reports to in
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