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Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of "antigen multi-copy display" and "calcium carbonate (CaCO3) biomineralization" to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

In cancer immunotherapy, immune cells are the main force for tumor eradication. However, they appear to be dysfunctional due to the taming of the tumor immunosuppressive microenvironment. Recently, many materials-engineered strategies are proposed to enhance the anti-tumor effect of immune cells. These strategies either utilize biomimetic materials, as building blocks to construct inanimate entities whose functions are similar to natural living cells, or engineer immune cells with functional materials, to potentiate their anti-tumor effects. In this review, we will summarize these advanced strategies in different cell types, as well as discussing the prospects of this field. [ABSTRACT FROM AUTHOR]

By incorporating an artificial reactive oxygen species (ROS) generation mechanism, a biotic/abiotic integration is designed to improve the anti-tumor effect of neutrophils by artificially potentiating their ROS effector mechanism in a remotely controlled route. Specifically, the photosensitizer Ce6 is nano-packaged by the albumin BSA to achieve biocompatible and efficient integration with neutrophils (NEs). Reinfusion of the engineered NEs into 4T1 tumor-bearing mice led to more Ce6 accumulation in tumors relative to Ce6 nanoformulation. At the peak of accumulation, tumor illumination activates the embedded Ce6 for ROS generation and NETosis formation. Because of the ROS-intensified cytolytic effect, the growth of 4T1 tumors is inhibited significantly. The photo-controlled process largely avoids the off-target effects observed frequently in current cell therapies. The strategy directly generates ROS effector molecules with spatiotemporal precision. This engineering approach is able to potentiate the native capacity of immune cells independent of the tumor microenvironment. • The photosensitizer is nano-packaged by BSA to facilitate integration • Tumor accumulation is obtained by the inherent tumor-targeting ability of neutrophils • The cytolytic activity of neutrophils is intensified by artificial ROS generation • Intensified ROS generation can be mediated in a temporospatial manner Li et al. develop a biotic/abiotic integration mechanism to improve the cytolytic effect of neutrophils by incorporating a nano-photosensitizer in neutrophils. Through a direct synergistic effect of ROS generated by photo-activated nano-photosensitizers, the anti-tumor effect of neutrophils is improved significantly in a remotely controlled route. [ABSTRACT FROM AUTHOR]