Fig. 12.

Nanomaterials depleting TAMs for the treatment of HCC using oxygen.

(A) BSA, HHA, and Mn²⁺ synthesize BHM. BHM is loaded with DOX and ICG and prepared into BHMDI.

(B) BHMDI decomposes into MnO₂, ICG, and DOX in GSH and the acidic environment after being engulfed by TAMs. MnO₂ catalyzes H₂O₂ decomposition into O₂ and effectively alleviates tumor deficiency. Oxygen reduces the number of M2-type TAMs and significantly improves the efficacy of ICG-mediated PDT. In addition, DOX promotes cell death.

(C) Relief of hypoxia reduces M2-type TAMs. PDT induces ICD in HCC cells, releases tumor-associated antigens and DAMPs and promotes DC and effector T cell maturation. The combined application of BHMDI and anti-PD-1 exerts a good effect and further inhibits tumor growth.

(D) Representative fluorescence images reflecting HIF-1a levels in tumors receiving different treatments. Scale bar: 200 μm

(E) Photographs and H&E-stained images of lungs of mice receiving different treatments, and numbers of lung nodules in each group.

(F) Flow cytometry plots of CD11c⁺ F4/80⁺ CD206⁺ cells in tumors in different groups

(G) Flow cytometry plots of CD3⁺ CD4⁺ T cells in tumors in different groups

(H) Flow cytometry plots of CD3⁺ CD8⁺ T cells in tumors in different groups

(I) In vivo maturation and maturation rates of DCs in lymph nodes from mice in different groups [206]. Copyright 2022 Elsevier.

TAMs, Tumor-associated macrophages; HCC, Hepatocellular carcinoma; BSA, Bovine serum albumin; HHA, hydrazided hyaluronan; BHM, Manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles; DOX, Doxorubicin; ICG, Indocyanine green; BHMDI, DOX/ICG-coloaded BHM nanoplatform; GSH, Glutathione; PDT, Photodynamic therapy; DAMPs, Damage-associated molecular patterns; DC, Dendritic cell; PD-1, Programmed Cell Death Ligand-1; Near-infrared, NIR; H&E, Hematoxylin-eosin staining; DCs, Dendritic cells.