A. marginale mCherry mRNA

Zeolitic imidazolate framework-8 (ZIF-8) and its composites have a wide range of applications. However, ZIF-8-based nanocomposites are mainly used as carriers for biomolecule delivery, and the functions of metal ions and ligands are rarely used to regulate their biological functions. In this study, dendritic mesoporous organosilica nanoparticles (DMONs) with tetrasulfide bonds were used to partially confine the growth of ZIF-8 within the mesopores, thus forming a new nanocomposite for mRNA delivery. Each component in the resulting DMONs-ZIF-8 contributes to the mRNA delivery application, including high loading due to the positively charged ZIF-8 and large mesopores of DMONs, endosomal escape facilitated by the imidazole ring of ZIF-8, and long-term glutathione depletion mediated by zinc ions and tetrasulfide bonds. Taken together, DMONs-ZIF-8 exhibited enhanced mRNA translation and better transfection efficiency than commercial products and toxic polymer-modified DMONs in vitro and in vivo.

Here, the researchers evaluated the delivery of mCherry mRNA in BALB/c mice to avoid interference from autofluorescence. Each formulation was subcutaneously injected into the waist of BALB/c mice. After 48 hours, the DMONs-ZIF-8/mRNA (Figure 1A)-treated group showed stronger mCherry signals than the DMONs-PEI-mRNA complex, which was comparable to mice injected with the commercial product in vivo-jetPEI-mRNA. The mCherry signals in the DMONs-ZIF-8 group were mainly located in the superficial cervical lymph nodes, axillary lymph nodes, and inguinal lymph nodes, while the signals in some mice in the DMONs-PEI group were undetectable or limited to specific lymph nodes. The quantitative results of the average radiation efficiency of the signal sites were calculated and plotted in Figure 1B, where the radiation efficiency of mice treated with DMONs-ZIF-8 and in vivo-jetPEI was comparable. The main organs and lymph nodes of mice injected with DMONs-ZIF-8 were collected to further evaluate the transfection efficiency (Figure 1C). No obvious mCherry signals were detected in major organs, while the superficial cervical lymph nodes, axillary lymph nodes, and inguinal lymph nodes all showed strong fluorescence, which was consistent with the imaging results ( Figure 1A), indicating that DMONs-ZIF-8 can efficiently deliver mRNA expression to lymph nodes rich in immune cells.

Figure 1. In vivo mCherry mRNA transfection in BALB/c mice. (Wang Y, et al., 2021)