Table 1.
Various types of nMOFs used for vaccine or adjuvant delivery
| MOF | Target | Stimuli‐responsive cargo release | Payload and encapsulation | Outcomes/results | Ref. |
|---|---|---|---|---|---|
| ZIF‐8 | Antigen presenting cells (APCs) | pH‐responsive | Cytosine–phosphate–guanine (CpG) and ovalbumin (OVA) | Induction of a potent immune memory response, and strong humoral and cellular immunity in vitro and in vivo | [73] |
| Uio‐66 (biomineralized by calcium phosphate) | APC | pH‐responsive degradation of (CaP) exoskeleton and PO4 3−‐responsive DNA release | CpG | Stimulation of potent immunostimulation in living macrophage cells and upregulation in the stimulated secretion of cytokines (IL‐6, TNF‐α) | [74] |
| Eu3+–GMP | Tumor cells | pH‐responsive | CpG and OVA | Enhancement of antigen cross‐presentation and the recruitment of tumor‐killing immunocytes (CD8+ T cells and NK T cells) | [75] |
| ZIF‐8 | Tumor cells (cancer cell membrane coating) | pH‐responsive | catalase (CAT) and doxorubicin (DOX) | Combination of chemotherapy and immunotherapy (anti‐PD‐L1), downregulate the expression of hypoxia‐inducible factor 1α and programmed death ligand 1 (PD‐L1) | [76] |
| ZIF‐8 | Tumor cells | pH‐responsive | DOX | Combination of chemotherapy and avasimibe immunotherapy, enhancement of cytotoxic T lymphocytes (CTL) infiltration in tumors | [77] |
| ZIF‐8 (biomineralized by Al3+) | Lymph nodes | pH‐responsive | CpG and OVA | Enhancement of antigen cross‐presentation and induction of strong antigen‐specific humoral and CTL responses with minimal cytotoxicity | [63] |
| Uio‐66 | Bone cells (zoledronic acid (ZOL) modification) | – | CpG | Suppression of osteoclast‐mediated bone destruction and enhancement of polarization of tumor‐resident macrophages to M1 phenotype | [78] |
| MIL‐88A | – | pH‐responsive | Minicircle DNA(MC) encoding anti‐CD3/anti‐EpCAM‐bispecific T‐cell engager (MC.BiTE) | High in vivo expression product of the BiTE‐induced T‐cell‐mediated cytotoxicity against human ovarian cancer SKOV3 cells | [79] |
| Al3+, Ru3+, and 2‐aminoterephthalic acid | APC | PO43−‐responsive Al3+ release | – | PTT (Ru) cooperates with immune adjuvant (Al) and anti‐PD‐L1 to recruit and activate APC, stimulate T‐cell proliferation and activation | [75] |
| ZIF‐8 | Tumor cells (cancer cell membrane coating) | pH‐responsive | Nivolumab (NV) | Reducing immune‐related toxicity and increasing patient compliance of ICB and enhancement of antitumor activity due to the preferential accumulation and prolonged retention of NV | [80] |
| Eu3+–GMP | APC | pH‐responsive | OVA (loaded by MSN) and CpG | Induction of innate immunity and adaptive immune system to be biased toward the Th1‐type cellular immune response | [81] |
| ZIF‐8 (biomineralized by CaCO3) | APC (lysosome‐targeting aptamer) | pH‐responsive | Perforin and granzyme B | Perforin, granzyme B, and Ca2+ reprogrammed CD8+ T Cells to enhance the insufficient targeting of T cells to the tumor area | [82] |
| ZIF‐8 | Tumor cells | pH‐responsive | g‐C3N4–Au, CO2 | Combined with CO gas therapy, a light‐controllable release behavior of CO, which gradually aggravates the oxidative stress in tumor cells to induce ICD | [83] |
| ZIF‐8 | Tumor cells | pH‐responsive | Mitoxantrone (MIT) and hydralazine (HYD) | Introduction of an apoptosis‐to‐pyroptosis transformation with a potential disruption of MDSC‐mediated T‐cell paralysis | [84] |
| Uio‐66 | Tumor cells | PO4 3−‐responsive | NLG919 (IDO inhibitor) and chlorambucil‐based prodrug (CLB) | Inhibition of IDO activity by NLG919 reverses the immunosuppressive tumor microenvironment, chemotherapy drugs are precisely activated in the presence of near‐infrared light, triggering immunogenic cell death (ICD) | [85] |
| MOF‐5 (doped by Gd3+) | Tumor cells | pH‐responsive | – | Intracellular Zn2+ overload activates endoplasmic reticulum stress for ICD induction, Gd3+ modulates the cell signaling and immunosuppressive microenvironment | [86] |
| ZIF‐8 | Tumor cells | pH‐responsive | Gemcitabine (Gem) and d‐1‐methyltryptophan (d‐1‐MT) | NPs efficiently decrease OS cell viability and reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid‐derived suppressor cells | [87] |
| Zr4+–Fe–TCPP | M2‐like tumor‐associated macrophages (TAM) | – | Diclofenac (Dic) | Codelivery of Fe and Dic decreases the efflux by hepcidin/ferroportin signaling pathway, enabling enhanced intracellular accumulation for improved M2‐to‐M1 macrophage repolarization | [88] |
| ZIF‐8 | Tumor cells | pH‐responsive | curcumin (CUR) and BMS1166 | BMS1166 inhibits the interaction between PD‐1 and PD‐L1 and CUR induces autophagy to increase ICD | [89] |
| ZIF‐8 | Tumor cells | pH‐responsive | Tumor cells | The whole‐cell cancer vaccines (WCCVs) with WCCV‐in‐shell structure with enhanced immunogenicity ascribing from the surface‐exposed calreticulin to promote dendritic cell recruitment, antigen presentation, and T‐cell activation | [90] |
| ZIF‐8 | Bone marrow dendritic cells (BMDCs) | pH‐responsive | OVA and polyinosinic–polycytidylic acid (polyIC) | In combination with systemic checkpoint blockade at merely 10% dose of PD‐1 blockade monotherapy, exhibits synergetic effects that reverse the immunosuppressive tumor microenvironment and activate strong immune reaction | [91] |