A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer (H40-star-PLA-SS-PEG) based on Boltorn H40 core,poly(L-lactide) (PLA) inner-shell,and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction.The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance (NMR),Fourier transform infrared (FTIR),gel permeation chromatography (GPC),differential scanning calorimeter (DSC),and thermal gravimetric analysis (TGA).Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm.Interestingly,these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol (DTT),most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds.As a hydrophobic anticancer model drug,doxorubicin (DOX) was encapsulated into these reductive unimolecular micelles.In vitro release studies revealed that under the reduction-stimulus,the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release.Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells.Methyl tetrazolium (MTT) assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX.All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.
PANG Yan 1,LIU JinYao 1,SU Yue 1,ZHU BangShang 2,HUANG Wei 1,ZHOU YongFeng 1,ZHU XinYuan 1,2 & YAN DeYue 1 1 School of Chemistry and Chemical Engineering,State Key Laboratory of Metal Matrix Composites,Shanghai Jiao Tong University,Shanghai 200240,China 2 Instrumental Analysis Center,Shanghai Jiao Tong University,Shanghai 200240,China
A novel type of porous scaffold was fabricated from single protein nanogels. The nanogels with single protein as core and crosslinked polymer network as shell were prepared through a two-step procedure including surface acryloylation and in situ radical polymerization. The formation of single protein nanogels was verified by matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer, transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses. Subsequently, the porous scaffolds were fabricated through a solvent evaporating process of aqueous nanogel solutions. The porous scaffolds were characterized by Fourier transform infrared (FTIR), scanning electronic microscopy (SEM), atomic force microscopy (AFM), and fluorescence microscopy. Interestingly, the obtained porous nanogel scaffolds presented multi-level porous morphologies with macro and nano scale pores, providing better spaces and microenvironments than normal macro porous scaffolds. Cell proliferation assay of nanogels showed low cytotoxicity. Considering that both the protein species and polymer constitutes can be pre-designed and adjusted, these multi-level porous nanogel scaffolds are promising candidates for tissue culture applications.
