Redox- and Temperature-Controlled Drug Release from Hollow Mesoporous Silica Nanoparticles

• Published in: Chemistry : a European journal Vol. 19; no. 45; pp. 15410 - 15420
• Main Authors: Jiao, Yunfeng, Sun, Yangfei, Chang, Baisong, Lu, Daru, Yang, Wuli
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.11.2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents - chemistry; antitumor agents; Carriers; Chemistry; core/shell materials; Disulfides; drug delivery; Drug Delivery Systems; Drugs; Glycols; Humans; Leakage; mesoporous materials; Nanoparticles; Nanoparticles - chemistry; Oxidation-Reduction; Silicon dioxide; Temperature; nanoparticles; drug delivery; core/shell materials; mesoporous materials; antitumor agents
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201301060

A controlled drug‐delivery system has been developed based on mesoporous silica nanoparticles that deliver anticancer drugs into cancer cells with minimized side effects. The copolymer of two oligo(ethylene glycol) macromonomers cross‐linked by the disulfide linker N,N′‐bis(acryloyl)cystamine is used to cap hollow mesoporous silica nanoparticles (HMSNs) to form a core/shell structure. The HMSN core is applied as a drug storage unit for its high drug loading capability, whereas the polymer shell is employed as a switch owing to its redox/temperature dual responses. The release behavior in vitro of doxorubicin demonstrated that the loaded drugs could be released rapidly at higher temperature or in the presence of glutathione (GSH). Thus, the dual‐stimulus polymer shell exhibiting a volume phase transition temperature higher than 37 °C can effectively avoid drug leakage in the bloodstream owing to the swollen state of the shell. Once internalized into cells, the carriers shed the polymer shell because of cleavage of the disulfide bonds by GSH, which results in the release of the loaded drugs in cytosol. This work may prove to be a significant development in on‐demand drug release systems for cancer therapy. Stand and deliver! A core/shell structure, the core being a mesoporous nanoparticle and the shell being a disulfide‐linked oligo(ethylene glycol) copolymer, can be used as a dual‐responsive drug carrier. Leakage of the drug cargo into the bloodstream is avoided owing to the carrier's high volume phase‐transition temperature (VPTT). After internalization into cells, the polymer shell comes off through cleavage of the disulfide bonds by glutathione (GSH), thus releasing the drug (see figure).