posted on 2021-04-20, 13:07authored byQiuquan Cai, Jiahong Jiang, Hongjie Zhang, Pengfei Ge, Liu Yang, Weipu Zhu
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 PEG10k) 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.