Metabolic Reprogramming of NK Cells by Black Phosphorus Quantum Dots Potentiates Cancer Immunotherapy

Abstract

Low persistence, metabolic dysfunction in microenvironment, and tumor-derived immunosuppression of Natural killer (NK) cells in patients are greatly limited the successful clinical application of NK cell-based cancer immunotherapy. Interestingly, herein that human serum albumin-encapsulated black phosphorus quantum dots (BPQDs@HSA) can effectively augment antitumor efficacy of clinical patients-derived NK cell immunotherapy is found. As the donor of phosphate group, BPQDs@HSA binds with the protein of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1A) and activates the downstream PI3K-Akt and mTOR signaling pathways to reprogram cell metabolism of glycolysis and further promote the oxidative phosphorylation, sequentially maintains the cell viability and immunity of NK cells. And multiomics analysis is therefore conducted to reveal the underlying immunoregulation mechanisms, and that BPQDs@HSA can interact with the Toll-like receptor (TLR) on the NK cell surface and increase the expression level of mTOR, and thus activate downstream NF-𝜿B signalling pathways to regulate cytokine secretion and enhance immune tumoricidal is found. BPQDs@HSA can also enhance immune surveillance, relieve immune suppression, and inhibit tumor immune escape. Collectively, this study not only demonstrates a successful strategy for nanomedicine-potentiated immune-cancer therapy, but also sheds light on the understanding of interface between nanomedicine and immune cells activation.

Tumor Metabolism-Rewriting Nanomedicines for Cancer Immunotherapy

“…108,109 To enhance the NK cell-mediated innate antitumor immunity by reprogramming its cellular metabolism, a immunosensitizer (BPQDs@HSA) was constructed by encapsulating black phosphorus (BP) quantum dots (QDs) in human serum albumin (HSA) (Figure 5A, Table 2). 110 In this study, the author found that the BPQDs@HSA treatment enhanced the expression of TLR-5, TLR-9, and NF-κB in NK cells (Figure 5B). Notably, activation of NF-κB signaling was found to upregulate the secretion of cytokines (e.g., IFN-γ) by NK cells while decreasing the secretion of immune suppressive factors, such as IL-10 and TGF-β (Figure 5C).…”

“…Data were expressed as mean ± SD (* p < 0.05, ** p < 0.01). Reproduced with permission from ref . Copyright 2023 Wiley-VCH.…”

Emerging 2D pnictogens: a novel multifunctional photonic nanoplatform for cutting-edge precision treatment

“…7(g)). 114 BPQDs@HSA binds to PIP5K1A proteins, activating downstream PI3K-Akt and mTOR signaling pathways, reprogramming cellular glycolytic metabolism, and further promoting oxidative phosphorylation, thereby maintaining cell viability and immunity to NK cells. Multi-omics analysis showed that proteins associated with NK cell immune function were significantly upregulated by BPQDs@HSA (Fig.…”

Recent Advances in the Biological Responses to Nano-black Phosphorus: Understanding the Importance of Intrinsic Properties and Cell Types

“…Subsequently, the downstream NF-κB signaling pathway was activated, which could regulate the cytokine release and finally enhance the antitumor immune response. 72 3.4. Disturbance and Recovery of Kidney Function.…”

“…Similarly, BPDs were encapsulated into human serum albumin (HSA) by Chen et al, which could initiate the immune activation of natural killer (NK) cells by interacting with a Toll-like receptor (TLR) and upregulating the expression of mTOR. Subsequently, the downstream NF-κB signaling pathway was activated, which could regulate the cytokine release and finally enhance the antitumor immune response …”