Cyclic Hydrazide-Functionalized Poly(ethylene oxide) Frameworks for the Synthesis of pH-Cleavable Drug- Carriers and Their Applications for the Stabilization of Gold Nanoparticles

Abstract

In this paper, two different types of poly(ethylene oxide) (PEO) frameworks with different functional groups such as the thiol group and cyclic hydrazide in the α,ω&#8208

positions bearing “smartness” are introduced. These heterobifunctional PEOs are synthesized via different functionalization approaches using t&#8208

butoxy PEO. Heterobifunctional PEOs, both α&#8208

luminol&#8208

ω&#8208

thiol PEO and α&#8208

thiol&#8208

cyclic hydrazide PEO, are prepared by chain&#8208

end functionalization of the reactive t&#8208

butoxy PEOs. The chain&#8208

end luminol as a cyclic hydrazide is found to be effective to yield pH&#8208

responsive prodrugs from the reaction with doxorubicin (Dox) yielding corresponding Dox&#8208

tethered PEO. The active t&#8208

butoxy PEO&#8208

initiated block copolymerization of N&#8208

phenylmaleimide (N&#8208

PMI) in acetone yields a block copolymer controlled in the 3&#8208

to 5&#8208

units range of the N&#8208

PMI group. The deprotection of the t&#8208

butoxy group, followed by tosylation, thioacetylaton, and the Gabriel process, provides corresponding α&#8208

cyclic hydrazide PEO. The functionality yields are almost quantitative (over 98 mol%). Polymeric prodrugs such as Dox&#8208

tethered PEO and folate&#8208

conjugated PEO are successfully employed for the stabilization of gold (Au) nanoparticles. The resulting products are characterized by a combination of proton nuclear magnetic resonance (1H NMR) spectroscopic, ultraviolet (UV)&#8211

visible spectroscopic, Fourier transform infrared (FT&#8208

IR), transmission electron microscopic (TEM), and size&#8208

exclusion chromatographic (SEC) analysis.