In depth analysis of the in vivo toxicity of nanoparticles of porous iron(iii) metal–organic frameworks

Abstract

In vivo acute toxicity of high doses of nanoparticles of three different porous iron(III) carboxylate Metal-Organic Frameworks (nanoMOFs) was intravenously investigated in rats by evaluating their distribution, metabolism and excretion. All studied parameters (serum, enzymatic, histological, etc.) are in agreement with a low acute toxicity. The mechanism of degradation and excretion of the nanoMOFs has been evidenced and shows that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine or feces without metabolization and substantial toxicity.

Heparin‐Engineered Mesoporous Iron Metal‐Organic Framework Nanoparticles: Toward Stealth Drug Nanocarriers

“…In contrast, the higher concentration (250 µg mL −1 ) of both uncoated and hep_MIL-100(Fe) induced a similar and signifi cant oxidative stress after 24 h. This is in concordance with the reversible increase of oxidative stress, previously observed after the intravenous administration of high doses of MIL-100(Fe) NPs due to the higher hepatic iron concentration. [ 25 ] As previously mentioned, heparin coating plays a dual role in the avoidance of the recognition and the removal of the coated NPs from the blood through the phagocytic innate immune cells. This is obviously an advantage for drug carriers or contrast agents to allow longer circulation times, enabling their biodistribution to other organs than the reticuloendothelial system (RES), commonly involved in the removal of foreign NPs.…”

“…These results are in good agreement with the reported in vitro [ 51 ] and in vivo biocompatibility of MIL-100(Fe) NPs. [ 25 ] However, iron overload can be associated with oxidative stress toxicity. [ 52 ] To address this point, the production of Reactive Oxygen Species (ROS) was then evaluated on the human promyelocytic leukemia cell line (HL60) in contact with two different doses (25 and 250 µg mL −1 ) of uncoated and heparin-coated MIL-100(Fe) NPs at different times ( Figure S12, Supporting Information; see Experimental Section).…”

“…NPs of the mesoporous iron(III) trimesate MIL-100(Fe) have been selected and synthesized via a biologically and environmentally favorable method, [ 23,24 ] due to their lack of in vivo toxicity, [ 25 ] as well as for their ability to encapsulate and release biologically relevant cargoes and their interesting theranostics properties. [ 17,19,26 ] In essence, the ideal nanoMOFs coating should: (i) be selectively attached on the external surface while avoiding intrusion inside the porous; (ii) not interact with the encapsulated moieties; (iii) display suitable stability under physiological conditions; and fi nally (iv) enhance nanoMOF performances for bioapplications, such as improvement of their colloidal stability or modulate their biodistribution.…”

Porous, rigid metal(III)-carboxylate metal-organic frameworks for the delivery of nitric oxide

“…7 The well-known porous metal(II) dihydroxyterepthalates, denoted are 6 A 3 , (M = Fe, Cr; A = solvent molecules or counteranions) bearing Lewis acid sites, has shown great promise for NO adsorption and delivery, 7(a) albeit to a lesser extent than the 7(b),7(c) due to the lower toxicity (LD 50 = 30 g · kg −1 ) 8 and pharmaceutical acceptability of iron based structures.…”

“…8 In addition, a priori biocompatible MOFs, derived from endogenous cations (i.e., iron and calcium) and/or therapeutic active ligands, have also been synthesized. 5,9 Some of them have been denoted as BioMILs (Bioactive Materials from Institut Lavoisier), 10 with the ability of the porous nontoxic MOFs to adsorb and release in a controlled manner as demonstrated for a wide range of active molecules.…”