Radiotherapy combined with nano-biomaterials for cancer radio-immunotherapy

Abstract

Radiotherapy (RT) plays an important role in tumor therapy due to its noninvasiveness and wide adaptation. In recent years, radiation therapy has been discovered to induce an anti-tumor immune response, which arouses widespread concern among scientists and clinicians. In this review, we highlight recent advances in the applications of nano-biomaterials for radiotherapy-activated immunotherapy. We first discuss the combination of different radiosensitizing nano-biomaterials and immune checkpoint inhibitors to enhance tumor immune response and improve radiotherapy efficacy. Subsequently, various nano-biomaterials-enabled tumor oxygenation strategies are introduced to alleviate the hypoxic tumor environment and amplify the immunomodulatory effect. With the aid of nano-vaccines and adjuvants, radiotherapy refreshes the host's immune system. Additionally, ionizing radiation responsive nano-biomaterials raise innate immunity-mediated anti-tumor immunity. At last, we summarize the rapid development of immune modulatable nano-biomaterials and discuss the key challenge in the development of nano-biomaterials for tumor radio-immunotherapy. Understanding the nano-biomaterials-assisted radio-immunotherapy will maximize the benefits of clinical radiotherapy and immunotherapy and facilitate the development of new combinational therapy modality.

Keywords: Immunotherapy; Nano-biomaterials; Radio-immunotherapy; Radiotherapy; Tumor.

Fig. 1

Schematic diagram of the main mechanism of radiotherapy combined with nano-biomaterials for cancer radio-immunotherapy

Fig. 2

Nanomaterial-mediated radiotherapy combined with immune checkpoint inhibitors. a Schematic diagram of immune checkpoint blockade and abscopal effect of WO_2.9-WSe₂-PEG NPs-mediated RT. b, c Elements mappings image and AFM images of WO_2.9-WSe₂ NPs. d Tumors growth curves of mice model. Reproduced from ref 42. Copyright 2020, American Chemical Society. e Tumor growth curves and f survival rates of mice after different treatments. g Quantitative analysis of matured DCs after treatments. Reproduced from ref 43. Copyright 2023, American Chemical Society. h The magnified TEM image of FeWO_X NPs. i Fe 2p and W 4f XPS data of FeWO_X nanosheets in different binding-energy ranges. j The survival curves of mice model. Reproduced from ref 25. Copyright 2020, Wiley–VCH GmbH

Fig. 3

Nano-biomaterial-enabled regulation of the hypoxic and oxidation-stressed tumor microenvironment regulation for radio-immunotherapy. a Schematic illustration of enhancing anti-tumor immunotherapy by radioactive nano-oxygen generator. b Distant tumor growth curves of mice model. c The percentage of tumor-infltrating CD8⁺ T cells (G1: PBS + Surgery, G2: APPs-PEG + Surgery, G3: PBS + ¹⁷⁷Lu-APPs-PEG, G4: ¹⁷⁷Lu-APPs-PEG + APPs-PEG). d–f The immunofluorescence slices showing the expression of HIF-1α (d), c-Myc (e) and Ki67 (f) in tumors. Reproduced from ref 22. Copyright 2021, Elsevier Ltd. g M2-like macrophages (CD11b⁺F4/80⁺CD206⁺). h MDSCs (CD45⁺CD11b + Gr-1⁺). i, j The levels of IL-6 (i) and TNF-α (j) in tumors with different treatments as indicated. Reproduced from ref 59. Copyright 2023, Wiley–VCH GmbH

Fig. 4

Nano vaccines/adjuvants and tumor radio-immunotherapy. a Images of DSBs tested by γ-H2AX foci. b Tumor volume growth curves of mice. Reproduced from ref 74. Copyright 2023, Elsevier B.V. c Schematic diagram of RT + BNP to enhance APC uptake and activation. d, e Expression levels of CD25 in tumors with different treatments and analyzed by flow cytometry and gene expression. The tumor volume (f) and growth rates analysis (g) in the B78 melanoma model. Reproduced from ref 78. Copyright 2019, Wiley–VCH Verlag GmbH & Co. KGaA, Weinheim

Fig. 5

Innate immunity activated by biological materials for radioimmunotherapy. a CLSM imaging of the lysosomal escape of ovalbumin (OVA, green) in the presence of USLs, NonCSLs, and ACSLs in DCs after incubation for 12 h. The cells were stained with lyso-tracker (red). Scale bar, 20 µm. b Average tumor growth kinetics. c Survival of the mice. Reproduced from ref 85. Copyright 2021, Wiley–VCH GmbH. d Schematic diagram of combined chemotherapy, radiotherapy and immunotherapy using selenium nanoparticles. e Tumor volume of mice model after different treatments. f Confocal microscopy showing the tumor infiltration level of HLA-E (purple) and NK1.1(green). Reproduced from ref 30. Copyright 2020, Wiley–VCH Verlag GmbH & Co. KGaA, Weinheim