Smart Metal-Organic-Framework Nanomaterial for Lung Targeting

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Smart Metal-Organic-Framework Nanomaterial for Lung Targeting, Angew Chem Int Ed. 2017 Sep 28

 

In the last decades, material science has led to the development of new nanodevices with unprecedented properties to specifically target organ, tissue and/or cells. In many cases, these delivery systems have demonstrated improved drug pharmacological activity and less toxicity, due to changes in the pharmacokinetic and biodistribution profiles. Nevertheless, despite the large number and the great incidence and mortality of lung diseases, targeting this organ remains a challenge. In the last years, a promising strategy has emerged, consisting in the passive pulmonary targeting of drugs, based on the mechanical filtration throughout the thin capillary bed of the lungs of intravenously administered drug particles, avoiding hepatic first pass effect. Different types of particles have been tested so far, leading to an improved lung bioavailability of the drugs and, in some cases, an increased drug efficacy. However, as a consequence of the slow particles degradation, prolonged particles retention causes important inflammation due to emboli, aggravated in many cases by the need to administer large amount of transporter materials that show poor drug loading.

 

 

We describe here nanometric biodegradable mesoporous iron(III) polycarboxylate based metal-organic frameworks nanoparticles (nanoMOFs) with a crystalline porous structure associated to the unique property to behave as pH-responsive smart material to perform lung delivery. Indeed, after intravenous (i.v.) injection, at the near neutral pH of the blood, nanoMOFs form microsized aggregates with the adequate size to be retained within the capillaries of the lung. Then, likely due to a progressive material surface degradation, agglomerates quickly start to disassemble to produce the initial nanoMOF particles that can penetrate in the cells, continue to degrade and release the drug, resulting in the observed therapeutic effect in a pre-clinical model of lung metastasis. Noteworthy, optimal timing of reversible nanoMOFs aggregation/disaggregation is compatible with tissue physiology, solving the mentioned toxicity concerns. Moreover, nanoMOFs exhibit in general larger drug loadings, compared to other drug delivery systems, thus reducing the amount of carrier needed to reach the same drug concentration in target tissue.

 

 

Angew Chem Int Ed. 2017 Sep 28.

Despite high morbidity and mortality associated to lung diseases, addressing drugs towards lung tissue remains a pending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery. However, toxic issues, derived from the long-term presence of the particles must be overcome. We show here that by exploiting some of the ignored properties of nanosized metal-organic frameworks it is possible to achieve impressive antitumoral effects on experimental lung tumours, even without the need to engineer the surface of the material. In fact, it was discovered that, based on unique pH-responsiveness and reversible aggregation behaviors, nanoMOF was capable to target the lung tissue. At the neutral pH of the blood, the nanoMOFs form aggregates with the adequate size to be retained within the lung capillaries. Then, within 24 h they disaggregate and release their drug payload. This phenomenon was compatible with lung tissue physiology.

 

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Smart Metal-Organic-Framework Nanomaterial for Lung Targeting

 

 

Simon-Yarza T, Giménez-Marqués M, Mrimi R, Mielcarek A, Gref R, Horcajada P, Serre C, Couvreur P

 

Angew Chem Int Ed. 2017 Sep 28.

 

doi: 10.1002/anie.201707346