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Table 2 Summary and comparison of properties of NPs mentioned in this review

From: Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities

Classifications of NPs

NP name

Size (nm)

Materials

Advantages

Disadvantages

Organic NPs

Polymer-based cationic NPs

100–200

Polymers, such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimers, chitosan, polyethylene glycol (PEG)

PAMAM enhances the loading capacity, protects the cargo from degradation and lessens systemic toxicity. PEG enhances structural stability, electrostatic binding, and hydrophobicity, and can be tuned to specifically meet the cargo delivery requirements. PEI exploits a large positive surface charge in gene transfection

Some evidence of cytotoxicity and side effects due to residual material aggregation in tissues. Elimination routes and in vivo metabolism have not been elucidated

Inorganic NPs

Nanodiamonds (NDs)

2–8

Carbon with truncated octahedral architecture

Low cost, fluorescent capability, low cytotoxicity, and provides long-term stability without causing cell death and oxidative stress

There exist differences and complications in characterizing NDs in dry state and in living organisms. Few in vivo studies done

Inorganic NPs

Gold NPs

1–100

Gold

Excellent chemical stability, good biocompatibility, tunable size, and large specific surface area

More information about uptake, biocompatibility and low cytotoxicity is required for clinical translation

Inorganic NPs

Graphene oxide NPs

165

A single-layer graphene oxide sheet (graphene is a layer of carbon arranged in a 2D crystal structure)

High surface area, mechanical and chemical stability, and biocompatibility. Able to directly penetrate the cell membrane or enter the cell through endocytosis

Some evidence of dose-dependent cytotoxicity and cell apoptosis

Inorganic NPs

Artificial virus NPs

130–135

Virus-like core (composed of plasmid DNA, condensing agent, and functional peptides) and a hydrophilic shell

Improved infection capacity; naturally occurring nanomaterials and hence biocompatible and biodegradable

Further modifications are necessary to improve the delivery efficiency in vivo

Inorganic NPs

Supramolecular NPs (SMNPs)

110–127

PAMAM, PEI, and TAT, assembled through specific non-covalent interactions and molecular recognition properties

Tunable particle size, optimizable surface charge, and enhanced delivery efficiency

More information about uptake, biocompatibility and low cytotoxicity is required for clinical translation

Inorganic NPs

Lipid-based cationic NPs

100–200

A mixture of cationic lipids (such as DOTAP, MVL5) and neutral lipids (such as DOPE, cholesterol)

Low toxicity, biodegradable, able to transport both hydrophobic and hydrophilic molecules

Crystallize after prolonged storage conditions, and poor diffusibility in the negatively charged vitreous due to excessive positive charges

Other NPs

DNA Nanoclews

56

Long-chain ssDNAs with palindromic sequences

Intrinsically biocompatible and degradable

More information about immune- related issues is required for clinical translation

Other NPs

Nanoscale zeolitic imidazole frameworks (ZIFs)

100–200

Made of divalent metal cations and imidazolate bridging ligands

3D network with a porous structure that facilitates endosomal escape

No known report on this delivery system for the retina yet