In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy

Abstract

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

Multifunctional Redox-Responsive Nanoplatform with Dual Activation of Macrophages and T Cells for Antitumor Immunotherapy

“…It had also been reported that activation of T cell-related immunity by nanomedicine could trigger a strong immune response and robust immune memory effects, which could effectively inhibit tumor growth for a prolonged period. 55,56 The macrophage results were in accordance with the immunofluorescence results. Compared with the PBS group, NPs loaded with motolimod significantly increased the expression of TNF-α and decreased the expression of CD206 on F4/80 + macrophages, while TNF-α and CD206 in the other groups showed no changes.…”

Manganese-Based Immunostimulatory Metal–Organic Framework Activates the cGAS-STING Pathway for Cancer Metalloimmunotherapy

“…Studies indicated that immune cell infiltration in the tumor microenvironment is closely related to tumor progression. , To investigate changes in the immune tumor microenvironment after the treatment, the mice were sacrificed on day 14, and the tumor-infiltrating immune cells were analyzed by flow cytometry (Figure S9b). The results showed that the number of APCs (Figure g,h) in the tumors after G5 treatment was significantly higher than that of other treatments, indicating the induction of an immunostimulatory tumor microenvironment after ISAMn-MOF treatment without causing body weight loss in the mice (Figure S9c).…”

In situ Engineering of Tumor‐Associated Macrophages via a Nanodrug‐Delivering‐Drug (β‐Elemene@Stanene) Strategy for Enhanced Cancer Chemo‐Immunotherapy

“…[4,21,35] Therefore, we used a 2,7-dichlorofluorescein diacetate (H 2 DCF-DA) staining assay to monitor the intracellular ROS expression of the treated macrophages. [23,[36][37][38] Fluorescence microscope images showed that M2-like macrophages treated with STNSP or β-Elemene induced the generation of intracellular ROS in a dose-dependent manner (Figure 2a, 2b and S6). Moreover, STNSP@ELE-treated macrophages displayed the highest intracellular ROS level (Figure 2a and 2b).…”