Functionalized magnetic nanoparticles as a novel strategy for the treatment of diabetic retinopathy

Purpose Neuroprotection-based strategies may be exploited to treat diabetic retinopathy (DR). Our aim is to establish a method for magnetic nanoparticle (MNP)-mediated delivery of neuroprotectants to the retina, expecting a prolonged therapeutic action. In the first phase of this project, we assessed the bioavailability and bioactivity of the neuroprotectant octreotide (OCT), a somatostatin analog, delivered as OCT-MNP. Methods The effects of OCT-MNP and those of free OCT (fOCT) were evaluated in in vitro assays using human retinal endothelial cells (HRECs), in H2O2-treated ex vivo retinal explants, and in vivo in untreated or in kainate-injected mouse eyes. In the in vitro assays, vascular endothelial growth factor (VEGF)-induced HREC proliferation, migration and tube formation were assessed. In the ex vivo and in vivo models, qPCR, histochemical and immunohistochemical techniques were used. Results In HRECs, 1 µM OCT-MNP displayed the same efficacy of 1 µM fOCT in inhibiting VEGF-induced changes. In H2O2-treated explants, both 1 µM OCT-MNP and 1 µM fOCT inhibited apoptosis. In particular, the efficacy of OCT-MNP was detected at concentrations as low as 0.001 µM. After intraocular injection in mouse eyes, OCT-MNP were localized to the retinal pigment epithelium and they did not induce any apoptotic sign in the retina. 1 µM OCT-MNP or fOCT co-delivered via intraocular injection with 100 µM kainate similarly protected the retina from apoptosis. Conclusions OCT-MNP maintain the functional properties of fOCT, in particular its neuroprotective capabilities. Intraocularly injected OCT-MNP are not toxic. They penetrate the retina, where they may release OCT in a sustained manner. Although needing confirmatory observations, these preliminary data are encouraging for a possible use of MNP-mediated drug delivery to treat DR.