Self-Assembly of a Diblock Copolymer with Pendant Disulfide Bonds and Chromophore Groups: A New Platform for Fast Release

Abstract

An amphiphilic block copolymer comprising poly(ethylene glycol) (PEG) and poly(2-(methacryloyl)oxyethyl-2'-hydroxyethyl disulfide) (PMAOHD) blocks was synthesized by atom transfer radical polymerization (ATRP). Pyrenebutyric acid was conjugated to the block copolymer by esterification, and a block copolymer with pendant disulfide bonds and pyrenyl groups (PEG-b-P(MAOHD-g-Py)) was obtained. (1)H NMR and gel permeation chromatography (GPC) results demonstrated the successful synthesis of the block copolymer. The cleavage of the disulfide bonds and the degrafting of the pyrenyl groups were investigated in THF and a THF/methanol mixture. Fluorescence spectroscopy, GPC, and (1)H NMR results demonstrated fast cleavage of the disulfide bonds by Bu(3)P in THF. Fluorescence results showed the ratio of the intensity of the excimer peak to the monomer peak decreased rapidly within 20 min. GPC traces of the block copolymer moved to a long retention time region after addition of Bu(3)P, indicating the cleavage of the disulfide bonds and the degrafting of the pyrenyl groups. PEG-b-P(MAOHD-g-Py) can self-assemble into micelles with poly(MAOHD-g-Py) cores and PEG coronae in a mixture of methanol and THF (9:1 by volume). The dissociation of the micelles in the presence of Bu(3)P was investigated. After cleavage of the disulfide bonds in the micellar cores, a pyrene-containing small molecular compound and a block copolymer with pendant thiol groups were produced. Transmission electron microscopy (TEM), dynamic light scattering (DLS), and (1)H NMR were employed to track the dissociation of the polymeric micelles. All the techniques demonstrated the dissociation of the micelles and the fast release of pyrenyl groups from the micelles.

Copolymer of poly(ethylene glycol) and poly(l-lysine) grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery

“…Aer graing lPEI onto PPL, the resonance peak around 2.93-3.23 ppm was signicantly strengthened and broadened, due to the fact that the 1 H NMR resonance peaks of the methylene groups from lPEI appeared around this location. 9 The triplet around 2.51 and 2.80 ppm attributing to DTDPA was signicantly strengthened, 34 demonstrating the conjugation of lPEI as well. In the FTIR spectra of PPL and PLI (Fig.…”

Reduction-sensitive polymeric nanocarriers in cancer therapy: a comprehensive review

“…2,2′-Dithiodiethanol-linked nanocarriers. Currently, various types of reduction-sensitive polymers based on the 2,2′-dithiodiethanol linkage have been exploited, such as brush block polymers, 57 graft block polymers, 44,58 linear block polymers, 42,77 and others. For example, Zhang et al synthesized a prodrug polymer based on mPEG and CPT by utilizing 2,2′-dithiodiethanol as a linkage through the radical addition-fragmentation chain transfer (RAFT) reaction and esterification reaction.…”

Thiol-responsive gemini poly(ethylene glycol)-poly(lactide) with a cystine disulfide spacer as an intracellular drug delivery nanocarrier

“…Therefore, polymeric micelles containing disulfide bonds have been prepared for redox-responsive drug delivery [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. These assemblies exhibit the controlled release of encapsulated drugs through the cleavage of disulfide bonds, causing destabilization or disintegration of the micellar aggregates.…”