*4.5. Light-Responsive Delivery System*

The surface of MSN can be decorated introducing photo-cleavable linkers for triggering the cargo release from MSN, by applying lights with di fferent wavelengths (ultraviolet, visible or near-infrared) [187,188]. Among all, as ultraviolet (UV) radiation has the highest power to easily break the bond, it has been the most commonly used light stimulus for the controlled drug release from MSN [187]. It has been reported that MSN coated with photo-responsive azobenzene-modified nucleic acid can trigger the drug release under UV light radiation [189]. However, the biomedical application of the UV light becomes restricted due to its toxicity and low tissue penetrability [190,191]. As an alternate, visible (Vis) light can be employed, as it is less harmful and has a higher tissue penetrability. Few Vis light-triggered MSN drug delivery systems have been reported [192,193]. For example, light responsive porphyrin nanocaps have been used to decorate the MSN. Porphyrin nanocaps are anchored via reactive oxygen species (ROS)-cleavable linkages, so that in response to the Vis light singlet oxygen molecules will be generated to break the sensitive linker and trigger the drug release by opening the pore of MSN [193].

Even though there are several advantages of using light (such as its easy application, non-invasiveness, low toxicity and precise focalization in the desired place), light-responsive delivery is restricted by its low tissue penetration capability (only a few millimeters). It has been observed that the best wavelengths for satisfactory tissue penetration are within the biological spectra, typically 800–1100 nm [134]. Likewise, Guardado-Alvarez et al. have exploited photolabile coumarine-molecules in the capping moiety of MSN surface to control the cargo release upon two-photon excitation at 800 nm [194]. Furthermore, Croissant and colleagues have shown that they can control drug release via a photo-transducer from mesoporous silica nanoimpellers in human cancer cells using two-photon light [195].
