Table 1 Summary of representative retinal nanomedicine for frontier applications
From: Frontier applications of retinal nanomedicine: progress, challenges and perspectives
Applications | Composition of nanomaterials | Cargos | Route | Functions | Authors and the year of publication | Current stage of application |
|---|---|---|---|---|---|---|
Natural organic nanomaterial-based eye drops | Fluorocarbon-modified chitosan-based nanocomplexes | Anti-VEGFA proteins or anti-PDL1 drugs | Eye drops | Via conjunctiva-sclera/blood-choroid-retina pathways, inhibited vascular proliferation and tumor growth | Zhuang Liu et al., 2023 [42] | In vitro and animal studies |
Chitosan and crosslinked with polyacrylic acid | Dexamethasone | Eye drops | Suppressed pain and inflammation post-ocular surgery | Investigators not provided; last update posted at 2021 | Phase III clinical trial (NCT03192137) | |
Chitosan-HA nanoparticles | Erythropoietin | Eye drops | Enabled erythropoietin delivery to the retina of glaucomatous rats and promoted an earlier retinal recovery | Esmeralda Delgado et al., 2023 [55] | In vitro and animal studies | |
Smart supramolecular peptides | / | Eye drops | Specifically identified and captured pro-angiogenesis to alleviate pathological retinal angiogenesis in DR mice | Bo Hu et al., 2023 [58] | In vitro and animal studies | |
Cell penetrating-peptide-based nanoparticles | Melphalan | Eye drops | Penetrated dense blood vessels of sclera to treat RB | Gang Wei et al., 2022[64] | In vitro and animal studies | |
Cyclodextrin nanoparticle | Dexamethasone | Eye drops | Significantly improved visual acuity and decreased macular thickness in patients with DME | Einar Stefánsson et al., 2015 [36] | Clinical trial (number not provided) | |
| Â | Cyclodextrin nanoparticle | Dexamethasone | Eye drops | Showed high biosafety and efficiency in patients with DME | Investigators, not provided, last update posted at 2022 | Phase II clinical trial (NCT05343156) |
Synthetic organic nanomaterial-based eye drops | Thermosensitive triblock copolymer | Hydrophilic and hydrophobic drugs | Gelling drops | Prolonged ocular surface contact and drug absorption | Laura M Ensign et al., 2020 [69] | In animal studies |
Nanomicelles | Aflibercept | Eye drops | Penetrated via corneal-scleral routes, remarkably inhibited anti-angiogenic activity in CNV | Xian Jun Loh et al., 2022 [84] | In vitro and animal studies | |
Nanoemulsion | Latanoprost and α-tocopherol | Eye drops | Prolonged ocular retention and enhanced retinal permeability for glaucoma treatment | Jian You et al., 2023 [90] | In vitro and animal studies | |
Liposomes | Conbercept | Eye drops | Inhibited CNV with high biosafety and achieved an equivalent effect to a single intravitreal injection | Xueying Ding et al., 2024 [100] | In vitro and animal studies | |
Solid lipid nanoparticles | Clarithromycin | Eye drops | Improved ocular permeation and drug therapeutic effect in endophthalmitis model | Pottathil Shinu et al., 2021 [102] | In animal studies | |
Liposomes | Triamcinolone acetonide | Eye drops | Improved visual acuity and diminished central foveal thickness in patients with DME | Arturo Santos et al., 2021 [107] | Phase I clinical trial (number not provided) | |
Inorganic nanomaterial-based eye drops | Carbon dots | Aflibercept | Eye drops | Enabled noninvasive intraocular concentration monitoring by the inherent fluorescence of carbon dots and inhibited angiogenesis | Yossi Mandel et al., 2019 [111] | In vitro and animal studies |
Magnetic nanoparticles | Guanabenz and valproic acid | Eye drops | Enabled noninvasive retinal drug imaging and targeted photoreceptors to protect retinal function | Vincent Marion et al., 2021 [113] | In animal studies | |
Hollow ceria nanoparticle | Pilocarpine | Eye drops | Improved intraocular drug delivery and intrinsic therapeutic activity of drug | Jui-Yang Lai et al., 2020 [114] | In vitro and animal studies | |
Gold nanoparticles | Large macromolecules | Eye drops | Effectively reach the retina layers with high biosafety | Nathan Ravi et al., 2021 [116] | In vitro and animal studies | |
Nanomaterial-based retinal contrast agents | Ultraminiature chain-like gold nanoparticle clusters | / | Intravenous injection | Achieved photoacoustic and optical coherence tomography imaging to visualize CNV | Yannis M Paulus et al., 2023 [127] | In animal studies |
Silicone elastomer contact lens | / | Repeated wearing | Emitted by far near-infrared light, and reduced retinal vascular hyper-permeability in DR rabbit model | Sei Kwang Hahn et al., 2022 [137] | In animal studies | |
MnO2 nanosponge | RB-targeted DNA aptamers |  | Targeted two different mRNAs, and realized fluorescence/magnetic resonance bimodal imaging and dual-gene therapy | Shanni Hong et al., 2024 [138] | In vitro and animal studies | |
AuNCs-conjugated with Fe3O4 nanoparticles | Muramyl dipeptide and perfluoropentane | Intravenous injection | Enhanced photoacoustic, ultrasound, and magnetic resonance imaging-guided low-intensity focused ultrasound /immunosynergistic therapy of RB | Xiyuan Zhou et al., 2020 [145] | In vitro and animal studies | |
Inorganic nanomaterial-based retinal therapeutic agents | Platinum nanozyme | / | Intravitreal injection | Suppressed hypoxia-induced abnormal neovascularization and facilitated retinal avascular normalization | Zhenglin Yang et al., 2022 [154] | In vitro and animal studies |
Cerium oxide nanoparticles | / | Eye drops | Penetrated via conjunctiva transscleral-retina pathway, inhibited inflammation and oxidative stress in AMD mouse model | Josep GarcÃa-ArumÃÂ et al., 2023 [265] | In vitro and animal studies | |
Prussian blue analogue KCa[FeIII (CN)6] nanoparticles | / | Intravitreal injection | Rescued retinal structures and visual function by ferroptosis inhibition in AMD mouse model | Ping Gu et al., 2021 [162] | In vitro and animal studies | |
Fe-N4-based single-atom nanozymes | / | Intravitreal injection | Performing catalase-like catalysis and eliminating pathological angiogenesis in retinal vasculopathies | Kelong Fan et al., 2022 [166] | In vitro and animal studies | |
Organic nanomaterial-based retinal therapeutic agents | MSC-EVs | / | Intravitreal injection | Improved retinal function and alleviated retinal apoptosis, inflammation, and angiogenesis in rats with DR | Hui Qian et al., 2024 [178] | In vitro and animal studies |
MSC-EVs | / | Intravitreal injection | Promoted healing of macular holes | Xiaomin Zhang et al., Last update posted at 2021 | Phase I clinical trial (NCT03437759) | |
MSC-EVs | / | Subtenon injection | Rescued visual functions for 6 months in patients with RP | Kuddusi Erkılıç, et al., Last update posted at 2022 | Phase II/III clinical trial (NCT05413148) | |
Synthetic melanin-like nanoparticles | / | Intravenous injection | Accumulated in the RPE for 3 months upon a single-dose application, and alleviated oxidative stress | Zongchao Han et al., 2022 [185] | In vitro and animal studies | |
Hybrid cell-membrane-cloaked nanoparticles | / | Intravenous injection | Decreased VEGF, protected from phagocytosis by macrophages, and enhanced accumulation in CNV region | Yuanyuan Su et al., 2021 [188] | In vitro and animal studies | |
Retinal nanomedicine-based gene therapy at early RD | HA nanospheres | Plasmid DNA carrying a GFP reporter gene | Intravitreal injection | Showed widespread gene expression in RPE | Muayyad R Al-Ubaidi et al., 2024 [193] | In animal studies |
Peptide-guided lipid nanoparticles | mRNA | Intravitreal injection | Observed robust protein expression in neural retina | Gaurav Sahay et al., 2023 [197] | In animal studies | |
Supramolecular nanoparticle vectors | CRISPR-Cas9 genome and Retinoschisin 1 DNA plasmid | Intravitreal or subretinal injection | Enabled CRISPR/Cas9-mediated gene knockin for treating X-linked juvenile retinoschisis | Shih-Hwa Chiou et al., 2020 [200] | In animal studies | |
Glutathione-responsive silica nanoparticles | Biomacromolecules (e.g., mRNA or ribonucleoprotein) | Intravenous or subretinal injection | Effectively delivered mRNA and ribonucleoprotein to RPE for gene therapy and genome editing | Shaoqin Gong et al., 2021 [204] | In vitro and animal studies | |
Retinal nanomedicine-assisted stem cell-based therapy at RD progression | HA-methylcellulose-based hydrogel | RPE and photoreceptors | Subretinal injection | Promoted vision respire in blind mice with advanced RD | Molly S Shoichet et al., 2020 [210] | In vitro and animal studies |
Gellan gum/silk sericin hydrogels | RPE | / | Supported RPE growth, enhanced cell proliferation and differentiation | Gilson Khang, et al., 2022 [215] | In vitro studies | |
Electrospun poly(glycerol sebacate)/poly(ϵ-caprolactone) biopolymer | Ciliary neurotrophic factor | / | Mimicked natural extracellular matrix and increased neurite extensions of RGC | Maksym Rybachuk et al., 2024 [219] | In vitro studies | |
Niobium carbide nanosheets | RPCs | Subretinal injection | Improved retinal neuronal differentiation of RPCs and protected RPCs by scavenging free radicals | Gu Ping et al., 2023 [222] | In vitro and animal studies | |
Retinal nanomedicine-based retinal optogenetics at late RD | Gold nanorods | / | Subretinal injection | Near-infrared stimulation increased activity in retinal neurons, and enabled mice to perform a learned light-driven behavior | Botond Roska et al., 2020 [230] | In animal studies |
UCNPs- graphene channelrhodopsin-2 biohybrid sensor | / | / | UCNP and optogenetically engineered cells on a graphene transistor for infrared sensing and imaging | Lianqing Liu et al., 2023 [231] | In animal studies | |
Retinal nanomedicine-based retinal prostheses at late RD | Molybdenum disulfide-coated optical synapses | / | Subretinal implants | Improved image sensing and learning functions | PingAn Hu et al., 2021 [250] | In vitro studies |
P3HT NPs | / | Subretinal injection | NPs spread out over the entire subretinal space, promoted light-dependent activation and recovered visual responses in late RD | Fabio Benfenati et al., 2020 [240] | In animal studies | |
P3HT NPs | / | Subretinal injection | Reinstated physiological signals at cortical level and visually driven activities in late RD rats bearing fully light-insensitive retinas | Fabio Benfenati et al., 2022 [241] | In animal studies | |
Quantum dots | / | Intravitreal injection | Converted light to electrical stimulus and improved mean best corrected visual acuity in patients with RP | Jeffrey Olson et al.,2021 [239] | Phase I clinical trial (NCT04008771) |