Table 3.
Histidine/imidazoles conjugated to non-biodegradable and biodegradable polymers.
| Polymer | Nucleic Acid | In Vitro /In Vivo |
Comment | Reference |
|---|---|---|---|---|
| NON-BIODEGRADABLE | ||||
| Histidinylated linear PEI (H-lPEI) | pDNA | Y/N | High transfection efficiency with lower toxicity than linear PEI (IPEI) in vitro | [55] |
| H-lPEI/IPEI | pDNA | Y/N | H-lPEI/IPEI with 57 and 67% lPE had similar transfection but lower toxicity than IPEI. | [56] |
| PAMAM-G4-H3-R | pDNA | Y/N | Histidine-arginine peptide conjugated to polyamidoamine dendrimer had higher transfection and lower toxicity than PEI in various cell lines | [57] |
| BIODEGRADABLE | ||||
| Urocanic acid (UA)-modified chitosan | pDNA | Y/N | DNA transfection efficiency in 293T cells was enhanced with the addition of UA to chitosan. | [58] |
| pDNA | N/Y | UA chitosan in complex with plasmid expressing PTEN via aerosol reduced number of lung tumors in a K-ras mouse model | [59] | |
| H6R6-modified chitosan (CS) | siRNA | Y/Y | Modified CS has higher transfection efficiency and improved endosomal escape. Modified CS carrier of survivin siRNA reduced breast cancer growth in vivo. | [60] |
| Histidine-cysteine modified trimethyl CS | pDNA | Y/Y | Histidine-modified CS polyplexes modestly increased transfection compared to unmodified CS polyplexes but histidine-polyplexes had lower transfection than arginine-modified CS polyplexes. | [61] |
| Imidazole-modified cyclodextrin (imCDP) | pDNA | Y/N | imCDP confers increased binding to DNA, enhanced released in acidic environments, increased buffering capacity and transfection efficiency in vitro. | [62] |
| Imidazole modified-curdlan | pDNA/ siRNA | Y/N | Enhanced endosomal escape and efficiently delivered plasmid and siRNA into cancer cells | [63] |
| Poly(imidazole-DMAEA) phosphazene (PIDP) | pDNA | Y/N | DNA transfection in 293T, COS-7 and Hela cells was higher with PIDP than the polymer control and PEI-25 kD, and had lower cytotoxicity. | [64] |
| End-Capping of modified PBAE | pDNA | Y/Y | End-capping of the PBAE polymer, C32, with histidine showed reduced transfection compared to end-capping with primary and tertiary amines. | [65] |
| siRNA-aptamer chimeras with polyhistidine | siRNA | Y/N | A platform for siRNA with a targeting aptamer, a dsRNA binding domain and polyhistidine for endosomal escape. Polyhistidine domain with 18 histidines more effective than 6 histidines. | [66] |
PEI, polyethyleneimine; pDNA, plasmid; PAMAM-G4, generation 4 polyamidoamine dendrimer; UA, urocanic acid; CS, chitosan; siRNA, short interfering RNA; imCDP, imidazole-modified cyclodextrin; DMAEA, dimethylaminoethylamino; PIDP, poly(imidazole/DMAEA) phosphazene; PBAE, poly(β-amino esters); dsRNA, double-stranded DNA binding domain.