Protein Nanogels with
Temperature-Induced Reversible Structures and Redox Responsiveness
Zhang, Y (Zhang, Yue)[ 1,2 ] ; Zhang, JM (Zhang, Jiamin)[ 3 ] ; Xing, C (Xing, Cheng)[ 3 ] ; Zhang, MM (Zhang, Mingming)[ 4,5 ] ; Wang, LY (Wang, Lianyong)[ 3 ] ; Zhao, HY (Zhao, Hanying)[ 1,2 ]
ACS BIOMATERIALS SCIENCE & ENGINEERING, 2016, 2(12): 2266-2275
DOI: 10.1021/acsbiomaterials.6b00490
WOS:000389789200016
Abstract:
There are many natural examples of smart structures that
are able to change conformations and functionalities responding to the external
stimuli. The responsiveness is directly related to their unique structures. In
the design of new materials, it is crucial to endow these materials with the
capabilities to change structures and functionalities under the external
stimuli. In this research, virus-mimicking protein nanogels with
temperature-induced reversible structures and redox responsiveness are
synthesized by cross-linking a thermally responsive polymer poly(di(ethylene
glycol) methyl ether methacrylate-co-2-(2-pyridyldisulfide) ethyl methacrylate)
with reduced bovine serum albumin (BSA) molecules through thiol-disulfide
exchange reaction. The lower critical solution temperature (LCST) and sizes of
the nanogels can be controlled by controlling the reaction conditions. The
nanogels are able to change their structures responding to the temperature
change. Below the LCST, BSA molecules are embedded inside the nanogels and
protected by the polymer chains. Above the LCST, polymer chains collapse
forming the cores, and BSA moves to the shells to stabilize the nanogels. The
disulfide-cross-linked nanogels are dissociated in the presence of glutathione.
In vitro cytotoxicity assays and cell uptake assays demonstrate that the
nanogels show low toxicity toward 3T3, 293T, and MCF-7 cells and can be
internalized into the MCF-7 cells. The nanogels will find applications in
protein delivery.