Table 1.

Nanomaterials in DR Treatment

Nanomaterials	Time	Diameter	Source	Loaded Drug		Efficacy			Existing Problems	Reference
CNE	2014	N/A	N/A	Hydrophilic/protein-based drugs		The retention time of drugs in the eyeball was prolonged and the adhesion of the mucus to the retina was enhanced through the electrostatic interaction with the human eye mucosa.				[50] [48]
SLN NLC	2013	288nm	Stearic acid, castor oil	Triamcinolone acetonide		Due to the good biocompatibility of physiological lipids, PEG loading further improves drug bioavailability in the eye and reduces drug irritation to the ocular mucosa and the occurrence of intraocular rejection.			The drug loading capacity is low, and the stability is poor during storage, which may lead to particle size growth and drug degradation.	[41] [50]–[55]
SiO2–CeCl3 nanoparticles	2014	130nm	N/A	N/A		Low-concentration silica-cerium (III) chloride (CeCl3) and α-crystal protein quickly form a preliminarily stable conjugate, inhibiting advanced glycation end products (AGEs) and restraining the production of intracellular reactive oxygen species as well as oxidative stress.				[42]
Silica nanoparticles	2012	N/A	N/A	N/A		Oxygen-induced abnormal retinal neovascularization is effectively reduced, and VEGF receptor-2 is induced to phosphorylate by restraining VEGF in vitro, thereby blocking the activation of ERK1/2 and inhibiting angiogenesis induced by VEGF in vitro.				[43]
AgNPS	2019	35nm	Mulberry leaf extract	N/A		AgNPS prepared by mulberry leaf extract using an environmentally friendly method have a satisfactory treatment effect on PR.			There is genotoxicity, which may be attributed to the elevated intracellular ROS induced by AgNPS and the resultant DNA damage.	[44] [56] [58]
GNP	2011	50nm	N/A	N/A		VEGFR-2 autophosphorylation induced by VEGF is suppressed, thereby inhibiting the activation of ERK1/2. No retinal toxicity is found, nor the viability of retinal microvascular endothelial cells is affected.			Cytotoxicity may occur as the particle size shrinks. A lot of experiments are needed to identify an appropriate particle size.	[39] [45]
MNP	2020	50nm	Iron oxide, ferric oxide	Octreotide		MNP has no toxicity to human retinal cells, and when combined with octreotide, it does not affect the anti-angiogenesis and anti-apoptosis effects of octreotide; MNP may be first located on the RPE and then on the entire retina.			Compared with other nanoparticles, magnetic iron oxide nanoparticles (MIONs) are less biologically toxic, but further studies are necessary to verify their safety.	[39] [57]
PLGA	2012 2013	20-250nm	Lactic acid, glycolic acid	Bevacizumab or other protein/enzyme drugs		PLGA is safe for the retina, widely used for drug delivery. PLGA nanoparticles can protect the protein from inactivation and aggregation in the presence of albumin.			The solubility in water is relatively poor, and the nanoparticles formed are large in size, so they tend to be cleared by the liver and spleen, reducing drug concentration in the retinal tissue.	[46] [47]
Chitosan-based nanoparticles	2014	N/A	N/A	N/A		Chitosan-based nanoparticles enable bevacizumab to be sustainedly released in the retina, thereby inhibiting retinal neovascularization.				[49]

Abbreviations: DR, diabetic retinopathy; CNE, cationic nanoemulsion; SLN, solid lipid nanoparticles; NLC, nanostructured lipid carrier; AgNPS, silver nanoparticles; GNP, gold nanoparticles; MNP, magnetic nanoparticles; PLGA, polylactic acid-glycolic acid.