Synthesis And Properties Of Bioreducible Trimethoxysilyl-ended Poly(ε-caprolactone)-b-Poly(Ethylene Glycol) Copolymers

Bioreducible core-cross-linked hybrid micelles were for the first time fabricated from biodegradable and biocompatible trimethoxysilyl-terminated and disulfide-bond-linked block copolymers poly(ε-caprolactone)-s-s-poly(ethylene glycol), which were prepared by combining thiol-ene click chemistry and ring-opening polymerization. The molecular structures, physicochemical, self-assembly, and bioreducible properties of these copolymers were thoroughly characterized by means of FT-IR, ~1H NMR, gel permeation chromatography, differential scanning calorimetry, wide angle X-ray diffraction, dynamic light scattering (DLS), and transmission electron microscopy. The core-cross-linking sol-gel reaction was confirmed by 1H NMR and thermogravimetric analysis, and the core-cross-linked hybrid micelles contained about 3 wt.% of silica. The bioreducible property of both uncross-linked and core-cross-liked micelles in 10 mM 1,4-dithiothreitol (DTT) solution was monitored by DLS, which demonstrated that the PEO corona gradually shedded from the PCL core. The anticancer doxorubicin drug-loaded micelles showed bigger size with nearly spherical morphology compared to blank micelles, presenting a DTT reduction-triggered drug-release profile at 37℃. Notably, the core-cross-linked hybrid micelles showed about two-fold drug loading capacity and a half drug-release rate compared to the uncross-liked counterparts. This work provides a useful platform for the fabrication of bioreducible core-cross-linked hybrid micelles potential for anticancer drug delivery system.