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Hierarchical bioresponsive nanocarriers for codelivery of curcumin and doxorubicin

Lin, Jian-Tao, Ye, Qing-Bang, Yang, Qing-Jin, Wang, Guan-Hai
Colloids and surfaces 2019 v.180 pp. 93-101
apoptosis, blood circulation, coatings, crosslinking, curcumin, disulfide bonds, doxorubicin, drug therapy, human cell lines, hydrogels, nanocarriers, neoplasm cells, neoplasms, pH, synergism
Hierarchical responsive nanocarriers have received much attention for targeted delivery of chemotherapeutics. In this study, we designed pH and redox dual-stage responsive nanocarriers in the different delivery stages for co-delivery phosphorylated curcumin (p-Cur) with doxorubicin (Dox). The MSNs nanocarriers were functionalized via specific cleavable PEGylation and hydrogel coating crosslinked by disulfide bonds: MSNs as core load Dox; p-Cur encapsulated in hydrogel coating. In blood circulation, PEGylation endow the nanocarriers with long time during blood circulation; while in tumor tissue, PEG shells could be cleaved due to the pH-sensitive bond and expose the cationic hydrogel coating to improve cell uptake; while inside tumor cells, hydrogel coating could be cleaved due to the GSH and release the drugs. The results showed that the dual-responsive shells endowed the nanocarriers with tumor extracellular pH-triggered cell uptake and specific cancer cell target release. The synergistic effects of the p-Cur and Dox enhanced cellular apoptosis in Hela cells.