Biomimetic Nanoplatform Loading Type I Aggregation-Induced Emission Photosensitizer and Glutamine Blockade to Regulate Nutrient Partitioning for Enhancing Antitumor Immunotherapy

Abstract

The intense metabolism of cancer cells leads to hypoxia and lack of crucial nutrients in the tumor microenvironment, which hinders the function of immune cells. We designed a biomimetic immune metabolic nanoplatform, in which a type I aggregation-induced emission photosensitizer and a glutamine antagonist are encapsulated into a cancer cell membrane for achieving specific delivery in vivo. This approach greatly satisfies the glucose and glutamine required by T cells, significantly improves the tumor hypoxic environment, enables the reprogramming of tumor and immune cell metabolism, induces immunogenic cell death, promotes dendritic cell maturation, and effectively inhibits tumor proliferation. Strong tumor-specific immune responses are further triggered, and the tumor immune-suppressing microenvironment is modulated, by decreasing the number of immunosuppressive cells. Moreover, subsequent combination with anti-PD-1 is able to generate strong abscopal effects to prevent tumor distant metastasis and provide long-term immune memory against tumor recurrence.

A Near-Infrared-II Fluorescent Nanocatalyst for Enhanced CAR T Cell Therapy against Solid Tumor by Immune Reprogramming

“…38 At the same time, activated CAR T cells also kill cancer cells by secreting a variety of cytokines, TNF-α and IFN-γ (Figure 8b,c), activating apoptosis signaling pathways, and inducing the body's powerful CAR T cell-mediated antitumor immune response. 34 HIF-1α served as a characteristic indicator reflecting the hypoxic environment. 27,50 The HIF-1α immunofluorescence stained sections of tumor tissues in the treatment group showed a weaker red fluorescence of HIF-1α than in the control group (Figure 8d), indicating that APHA@CM can relieve the hypoxic environment in tumor tissues.…”

Slimming and Reinvigorating Tumor‐Associated Dendritic Cells with Hierarchical Lipid Rewiring Nanoparticles

“…DC maturation can prime T cell responses. [52][53][54] Therefore, we tested the capacity of LPS-treated DCs to enhance CD8 + T cell proliferation upon lipid and NP exposure. We loaded the DCs with ovalbumin (OVA) 257-264, a peptide epitope to induce antigen cross-presentation, before coculturing them with the CD8 + T cells (Figure 3f).…”

Biomimetic Active Materials Guided Immunogenic Cell Death for Enhanced Cancer Immunotherapy

“…Reproduced with permission. [ 34 ] Copyright 2022, American Chemical Society. B) Homotypic membrane‐camouflaged biomimetic nanoplatform with gold nanocrystals (denoted as AuDRM) for photothermal‐induced ICD combined immunotherapy.…”

“…[32] RBC membranes does not endow any active targeting ability to tumor, the homotypic targeting capacity of cancer cell membranes was widely utilized for guiding ICD-agents fabrication. [33] Photosensitizers coated with cancer cell membranes can accumulate specifically at the tumor site, enhance the PDT [34] (Figure 2A) or PTT [35] (Figure 2B) induced ICD effect, and induce effective anti-tumor immune response to inhibit tumor growth. Surface modification of cancer cell membranes was also used for nano-chemo agents to reduce the clearance and realize tumor homologous targeting.…”

“…High CRT expression and increased secretion of extracellular HMGB1 and ATP was induced after CTTPA-G therapy. Reproduced with permission [34]. Copyright 2022, American Chemical Society.…”