Nanomedicines based on nanoscale metal-organic frameworks for cancer immunotherapy

Abstract

Cancer immunotherapy, with an aim to enhance host immune responses, has been recognized as a promising therapeutic treatment for cancer. A diversity of immunomodulatory agents, including tumor-associated antigens, adjuvants, cytokines and immunomodulators, has been explored for their ability to induce a cascading adaptive immune response. Nanoscale metal-organic frameworks (nMOFs), a class of crystalline-shaped nanomaterials formed by the self-assembly of organic ligands and metal nodes, are attractive for cancer immunotherapy because they feature tunable pore size, high surface area and loading capacity, and intrinsic biodegradability. In this review we summarize recent progress in the development of nMOFs for cancer immunotherapy, including cancer vaccine delivery and combination of in situ vaccination with immunomodulators to reverse immune suppression. Current challenges and future perspectives for rational design of nMOF-based cancer immunotherapy are also discussed.

Keywords: cancer immunotherapy; cancer vaccine; immune response; immunomodulators; in situ vaccination; nanoscale metal-organic frameworks (nMOFs).

Fig. 1. Schematic illustration of the application of nanosized metal-organic frameworks (nMOFs) in cancer immunotherapy.

These applications include vaccine delivery and in situ vaccination.

Fig. 2. Lymph node-targeting nMOFs as an efficient cancer vaccine delivery platform.

a Schematic illustration of Zn²⁺-based nMOFs containing aluminum adjuvant and OVA (ZANPs), and how they evoke efficient humoral and cellular immune responses. b In vivo near-infrared fluorescence imaging of different formulations at 1, 6, 12 or 24 h after administration in the footpad. c OVA-specific CTL response elicited by different formulations, based on flow cytometry of CFSE labeling. d Tumor volume from mice challenged with EG7-OVA (EL-4 thymoma tumor cells transfected with the OVA gene) cells. *P < 0.05, **P < 0.01, ***P < 0.001. CTL cytotoxic T lymphocyte, DCs dendritic cells, mIM imidazole, OVA ovalbumin, ZNP Zn²⁺-based nMOFs containing OVA but no adjuvant, ZANPs Zn²⁺-based nMOFs containing aluminum adjuvant and OVA. This figure was adapted with permission from ref. [48]. Copyright 2019 Elsevier B.V.

Fig. 3. A Zr₆-connected nMOF integrating a benzoporphyrin-based photosensitizer (TBP-nMOF) for photodynamic treatment (PDT) and combination immunotherapy.

a Proposed mechanism of antitumor immune responses induced by TBP-nMOF, and the synergy between photodynamic therapy and anti-PD-1 antibody to inhibit tumor metastasis. b, c Tumor volume changes after b photodynamic therapy (light) alone or c combined PDT with antibody against PD-1 (α-PD-1). d Percentage of CD8⁺ T cells that infiltrated the tumors after the treatments in c. e Bioluminescence images of the lung from mice bearing luciferase-expressing primary 4T1 tumors on the right back of hind leg region after various treatment; 1: PBS; 2: PBS + light + α-PD-1; 3: TBP-nMOF + α-PD-1; 4: TBP-nMOF + light; 5: TBP-nMOF + light + α-PD-1. **P < 0.01, ***P < 0.001. This figure was adapted with permission from ref. [70]. Copyright 2018 American Chemical Society.

Fig. 4. An Hf-based nMOF serve as radioenhancer, integrated low-dose radiation for immune response stimulation.

a Abscopal effect of nMOF-enhanced radiotherapy: Hf-based nMOF triggers immunogenic cell death, which releases tumor antigen serve as in situ vaccine, while anti-PD-1 antibody reverses the immunosuppressive tumor microenvironment, enhancing T cell expansion and tumor infiltration. DC, dendritic cells. b Growth of distant tumors after mice were injected different formulations bilaterally on the right back of hind leg region with CT26 colorectal tumor cells. c, d Primary and distant tumors were collected and analyzed for content of tumor-infiltrating DCs natural killer (NK) cells. This figure was adapted with permission from ref. [80]. Copyright 2018 Springer Nature.