Light-Responsive, Singlet-Oxygen-Triggered On-Demand Drug Release from Photosensitizer-Doped Mesoporous Silica Nanorods for Cancer Combination Therapy

• Published in: Advanced functional materials Vol. 26; no. 26; pp. 4722 - 4732
• Main Authors: Yang, Guangbao, Sun, Xiaoqi, Liu, Jingjing, Feng, Liangzhu, Liu, Zhuang
• Format: Journal Article
• Language: English
• Published: Blackwell Publishing Ltd 12.07.2016
• Subjects: Cancer; cancer treatment; Carriers; chlorin e6; Drug delivery systems; Drugs; Light irradiation; light-responsive drug release; Macromolecules; mesoporous silica nanorods; Nanorods; Polyethylene glycol; smart drug delivery systems
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201600722

Smart drug delivery systems with on‐demand drug release capability are rather attractive to realize highly specific cancer treatment. Herein, a novel light‐responsive drug delivery platform based on photosensitizer chlorin e6 (Ce6) doped mesoporous silica nanorods (CMSNRs) is developed for on‐demand light‐triggered drug release. In this design, CMSNRs are coated with bovine serum albumin (BSA) via a singlet oxygen (SO)‐sensitive bis‐(alkylthio)alkene (BATA) linker, and then modified with polyethylene glycol (PEG). The obtained CMSNR‐BATA‐BSA‐PEG, namely CMSNR‐B‐PEG, could act as a drug delivery carrier to load with either small drug molecules such as doxorubicin (DOX), or larger macromolecules such as cis‐Pt (IV) pre‐drug conjugated third generation dendrimer (G3‐Pt), both of which are sealed inside the mesoporous structure of nanorods by BSA coating. Upon 660 nm light irradiation with a rather low power density, CMSNRs with intrinsic Ce6 doping would generate SO to cleave BATA linker, inducing detachment of BSA‐PEG from the nanorod surface and thus triggering release of loaded DOX or G3‐Pt. As evidenced by both in vitro and in vivo experiments, such CMSNR‐B‐PEG with either DOX or G3‐Pt loading offers remarkable synergistic therapeutic effects in cancer treatment, owing to the on‐demand release of therapeutics specifically in the tumor under light irradiation. CMSNR‐B‐PEG acts as a drug delivery carrier to load with either small drug molecules or larger macromolecules. This work develops a novel approach to engineer smart on‐demand drug delivery/release systems responsive to long‐wavelength light with a rather low optical power, interesting not only for anti‐cancer chemotherapy, but also potentially for gene therapy or immunotherapy toward cancer or other diseases.