Reduction-Responsive Anticancer Nanodrug Using a Full Poly(ethylene glycol) Carrier

Poly­(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG₂₀₀ and PEG_10k) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.