Figure 3.

Common surface modifications of metal and metal oxides-based nanoparticles reported in siRNA delivery. (a) Magnetic nanoparticles (MNPs). Branched PEI polymer is utilized for preparation of magnetite nanoparticle clusters (MNCs) ⁶⁴, ⁶⁸. PEI is directly reacted with MNPs to form stable nanocomplexes or indirectly anchored through the covalent binging to 3,4-dihydroxy-L-phenylalanine (DOPA). N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) is applied to activate bovine serum albumin (BSA)-MnMEIO nanoparticles. The SPDP-activated MnMEIO nanoparticles are then treated with thiolated poly(ethylene glycol) (PEG) functionalized with a cyclic Arg-Gly-Asp (RGD) peptide, or thiolated siRNA at the distal end (red circle) ⁶⁷. MNPs can be coated with two different polymers of poly(oligoethylene glycol) methyl ether acrylate (P(OEG-A)) and poly(dimethylaminoethyl acrylate) (P(DMAEA)). P(DMAEA) forms an internal layer with a slight positive charge for electrostatic immobilization of siRNA and P(OEG-A) forms an outer antifouling shell for long circulation in vivo ⁶⁵. (b) Gold nanoparticles (AuNPs). Amine functionalized AuNPs are directly prepared by surface modification with cystamine hydrocholoride (CA) that carries amine-derived positive charge ⁷⁵. AuNPs modification with a positive charged polymer layer of PEI ⁷⁷ or triethylenetetramine (TETA) ⁷⁹ are reported for the simple electrostatic conjugation and delivery of siRNA. These modifications are commonly accomplished with Au-thiol non-covalent binding through thiol-terminated linkers such as 11-mercaptoundecanoic acid ⁷⁵, ⁷⁹.