Hematopoietic responses to metal-organic frameworks in adult mice following pulmonary exposure

Abstract

The metal-organic frameworks (MOFs) MIL-100 and NH₂-MIL-125 have hierarchical structure pores with high adsorption capacities and have therefore been suggested for drug delivery, gas storage, catalysis and chemical sensing. The widespread applications of these MOFs raise concerns about the possible release into the environment and subsequent human exposure. Yet, the available knowledge of the toxicity of these MOFs is rather scarce despite the encouraging applications. Here, we investigated the hematopoietic effects in different organs induced by MIL-100 and NH₂-MIL-125 in mice after intratracheal instillation. The hematopoietic cells in the bone marrow (BM), lungs, and spleen were analyzed through flow cytometry method. Compared to NH₂-MIL-125, MIL-100 triggered changes in more types of hematopoietic cells in the BM and spleen, but comparable changes in the lungs. In the BM and lungs, both the two MOFs suppressed myelopoiesis on day 1, but promoted myelopoiesis on day 7. In the spleen, by contrast, continuous suppressed myelopoiesis were found on day 1 and day 7. Moreover, changes in megakaryocyte progenitors (MkPs) were only detected in the lungs. These results unveil the potential disruption of hematopoietic homeostasis during inhalation of the two MOFs, which provided in vivo biological effect data for further evaluation of the biosafety of MOFs for future medical applications.