# Synthesis of Hydrogel-Based Microgels and Nanogels Toward Therapeutic and Biomedical Applications
## 4 Paradigm Shift: Bulk Hydrogels to Hydrogel Micro/Nanoparticles
### Designing Stimuli-Responsive Properties
#### 4.1.3 Light Sensitivity  
The photo-responsive property is represented by the benefits of light as a triggering signal, for their minimally destructive and highly penetrative nature to biological settings. Light-sensitive hydrogels utilize photosensitive agents or certain chemical structures which could absorb specific wavelengths of light and undergo structural or chemical changes. This mechanism is highly compatible with thermo-sensitive hydrogels and allows highly precise spatiotemporal control of external stimulation, making them suitable for in vivo targeted therapy and diagnostics [70,84,204].  
Photosensitivity can be categorized into photothermal and photochemical effects. Photothermal effects are based on the conversion of photo energy into heat, which rapidly dissipates into its vicinity and raises the local temperature. Combined with a thermo-responsive hydrogel, phase transition can be induced by the absorption of light instead of external heat, avoiding undesirable thermal damage, especially when the target location is far from externally accessible points like skin. Also, the effective penetration of light into tissue is deeper for near-infrared (NIR) or longer wavelengths of light than visible or ultraviolet, which offers a facile onset mechanism for non-invasive anticancer treatment [205,206]. Gold nanoparticles and carbon nanomaterials are the most utilized photosensitive agents for this purpose. Gold nanoparticles exhibit a unique phenomenon called the localized surface plasmon resonance (LSPR), which makes them effectively absorb a certain wavelength of light depending on its size [205]. The LSPR of gold nanoparticles can be tuned to absorb NIR light by synthesizing into a rod-shape and can induce synergistic effects for plasmonic photothermal therapy (PPTT) [70,123,207]. Basically, PPTT follows a stepwise mechanism starting from the selective accumulation of gold nanorods at the target followed by irradiation of an NIR laser, inducing highly effective absorption of photo energy and localized heat, which results in a sufficiently high temperature to induce cell damage and death [208,209].  
Photochemical effects utilize certain chemical bonds or functional groups that are directly affected by the absorption of certain light. Azobenzene or spiropyran groups can undergo reversible conformational changes, called photoisomerization [210,211]. Azobenzene can be \"photo-switched\" between _cis_- and _trans_-form by absorptions of UV and visible light, respectively, whereas spiropyran can form its open-ring isomer called merocyanine under UV and visible light. Both changes induce the changes in porosity, elasticity, and volume of the hydrogels [212,213]. Chemical functional groups like coumarin could form photo-cleavable bonds upon UV irradiation, making it suitable for photo-degradable hydrogel systems and on-demand drug release. Coumarin-functionalized polymers could be crosslinked via dimerization of two coumarin groups under UV light of around 360 nm and can be disconnected under deeper UV light of around 250 nm [214,215]. This approach provides the most direct manipulation of a hydrogel network structure, but the destructive effects and insufficient tissue penetration of UV light must be carefully considered.