Thermoresponsive Micelles from Oligopeptide‐Grafted Cyclotriphosphazenes

Abstract

Hard graft: Amphiphilic cyclic phosphazene trimers grafted with hydrophobic oligopeptide (red) and hydrophilic methoxypolyethylene glycol (blue) show a variety of thermoresponsive properties including lower critical solution temperatures near body temperature. They form strong micelles in aqueous solution at an appropriate hydrophobic‐to‐hydrophilic balance.

Nanoparticulate platinum(II) anticancer drug: Synthesis and characterization of amphiphilic cyclotriphosphazene–platinum(II) conjugates

“…The platinum(II) intermediates, cis-(CHA) 2 Pt(NO 3 ) 2 and cis-(CHA)(NH 3 )PtSO 4 , were prepared according to the literature methods [21,22]. The amphiphilic cyclotrophosphazene drug carriers, [NP(PEG550)(GlyPheLeuAspEt 2 )] 3 and [NP(PEG350)(GlyPheLeuMalEt 2 )] 3 were prepared following the procedure described in our previous work [19,20]. Tetrahydrofuran (THF) was dried by boiling at reflux over sodium metal and benzophenone and then distilled under argon atmosphere.…”

“…2 shows that platination results in broadening of the phosphorus resonance of the carrier probably due to molecular aggregations as just mentioned above. In our previous work [19], we have shown that the carrier cyclotriphosphazene molecules do not form micelles but exist as unimer in aqueous solution because of too high hydrophilicity of MPEG550 compared with the hydrophobicity of the tetrapeptide. However, it was found in the present study that platination of the same tetrapeptide with very hydrophobic dicyclohexyl platinum(II) moiety gave rise to strong molecular aggregations.…”

“…Dynamic light scattering (DLS) measurements were performed using Malvern Zetasizer (Nano-ZS). The micellar cyclotriphosphazene carrier, [NP(MPEG550)GlyPheLeuAsp(Et) 2 ] 3 (0.5 g, 0.15 mmol) prepared according to the author's procedure [19,20] was hydrolyzed by potassium hydroxide (0.11 g, 2.0 mmol) in methanol (20 mL) by stirring for 12 h at room temperature. The reaction mixture was concentrated under reduced pressure and then an excess amount of diethyl ether or hexane was added to induce precipitation.…”

“…Most recently, we have discovered that amphiphilic cyclotriphosphazenes grafted with hydrophobic oligopeptide ethyl esters instead of simple amino acids along with equimolar hydrophilic methoxy-poly(ethylene glycol) (MPEG) can afford to form stable micelles in aqueous solution [19,20]. These monodisperse trimers seem to be an excellent carrier for conjugation of the platinum complexes to make micellar or nanoparticulate anticancer drugs, since these trimers can be easily functionalized for platination by hydrolysis of the oligopeptide ethyl ester side group.…”

Amphiphilic Cyclotriphosphazenes Grafted with Branched Oligopeptides

“…[13][14][15] We have demonstrated in our previous study that these tripodal amphiphiles provide strong intra-and intermolecular hydrophobic interactions tunable for self-assembly to various nanostructures such as micelles, bilayered polymersomes, and molecular gels that are ruled by the hydrophobicity parameter (log P) of the oligopeptides employed. In particular, we have shown that the tripodal cyclotriphosphazenes bearing linear oligopeptides with high hydrophobicity (Log P > 1) remain as stable micelles in aqueous solution but those with intermediate hydrophobicity (0 < log P < 1) reassemble into bilayered polymersomes.…”