Red Light-Triggered Polyethylene Glycol Deshielding From Photolabile Cyanine-Modified Mesoporous Silica Nanoparticles For On-Demand Drug Release

PEGylation of drug delivery systems (DDSs) provides a promising approach to overcome the side effect of traditional chemotherapy via the enhanced permeability and retention (EPR) effect, although it further inhibits the internalization behavior of nanocarriers. PEGylation/dePEGylation of the nanocarriers at the desired site exhibits great advantages for nanocarrier-based on-demand drug release. Here, we reported a photoinduced polyethylene glycol (PEG) deshielding nano-carrier, SiO2@DOX-Cy-PEG, for on-demand drug release in an acidic tumor microenvironment. SiO2@DOX nanoparticles were functionalized with PEG-alkyne chains by click reaction with the photolabile cyanine-azide linkers. Under red light irradiation (650 nm), doxorubicin (DOX) can be effectively released from mesoporous silica nanoparticles (MSNs) due to the photolysis of Cy, resulting in the cleavage of the linkers and PEG deshielding in cancer cells. Therefore, SiO2@DOX-Cy-PEG nanoparticles with irradiation arouse a higher cell apoptosis and death ratio, further proving that dePEGylation of MSNs accelerates the release of DOX. In addition, the experiment of the antitumor effect in vivo demonstrated that dePEGylation of the SiO2@DOX-Cy-PEG could effectively promote the therapeutic effect on xenografted 4T1 tumor-bearing BALB/c mice. The results suggested that SiO2@DOXCy-PEG was a precisely and remotely on-demand drug delivery system controlled by red light.