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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]

Metabolic reprogramming allows tumor cells to prefer aerobic glycolysis as the main energy source, resulting in the massive accumulation of lactate in the tumor microenvironment (TME). It is found that lactate is no longer a waste product produced by glycolysis, but plays an important role in cancer progression. The modulation of lactate in the TME has become a promising target for cancer therapy. Although many small molecular inhibitors modulating the production or transport of lactate have appeared at present, their safety and efficacy have limited their further clinical application due to their non-specific targets and biodistribution. Studies have shown that nanomedicine has unique advantages, improving drug delivery efficiency and treatment efficacy while reducing damage to normal tissues, which greatly promotes the development of the research of nanosystems based on lactate modulation. In this review, we summarize the source and metabolism of lactate, the effect of lactate on the TME and recent advances in nanosystem-mediated strategies of lactate modulation for enhanced cancer therapy, hoping to provide ideas and directions for future research in related fields. [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]

Immunotherapy techniques, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cell therapies and cancer vaccines, have been burgeoning with great success, particularly for specific cancer types. However, side effects with fatal risks, dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy. Nano metal-organic frameworks (nMOFs), with an accurate structure and a narrow size distribution, are emerging as a solution to these problems. In addition to their function of temporospatial delivery, a large library of their compositions, together with flexibility in chemical interaction and inherent immune efficacy, offers opportunities for various designs of nMOFs for immunotherapy. In this review, we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies. We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation. Finally, a prospect of nMOFs in cancer immunotherapy will be discussed. [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]