The design of smart, photoactivated nanomaterials for targeted drug delivery systems (DDS) has garneredsignificant research interest due in part to the ability of light to precisely control drug release in specific cells ortissues with high spatial and temporal resolution. The development of effective light-triggered DDS involvesmechanisms including photocleavage, photoisomerization, photopolymerization, photosensitization, photothermalphenomena, and photorearrangement, which permit response to ultraviolet (UV), visible (Vis), and/or Near Infrared(NIR) light. This review explores recent advancements in light-responsive small molecules, polymers, andnanocarriers, detailing their underlying mechanisms and utility for drug delivery and/or imaging. Furthermore, ithighlights key challenges and future perspectives in the development of light-triggered DDS, emphasizing thepotential of these systems to revolutionize targeted therapies. A systematic literature search was performed using Google Scholar as the primary database and information source.We searched the recently published literature (within 15 years) with the following keywords individually and inrelevant combinations: light responsive, nanoparticle, drug release, mechanism, photothermal, photosensitization,photopolymerization, photocleavage, and photoisomerization. We selected 117 scientific articles to assess the strength of evidence after screening titles and abstracts. We foundthat six mechanisms (photocleavage, photoisomerization, photopolymerization, photosensitization, photothermalphenomena, and photorearrangement) have primarily been used for light-triggered drug release and categorized ourreview accordingly. Azobenzene/spiropyran-based derivatives and o-nitrobenzyl/Coumarin derivatives are often usedfor photoisomerization and photocleavage-enabled drug delivery, while free radical polymerization and cationicpolymerization comprise two main mechanisms of photopolymerization. One hundred two is the primary active radical oxygenspecies employed for photosensitization, which is a key factor that impacts the therapeutic effects in Photodynamictherapy, but not in photothermal therapy. The comprehensive review serves as a guiding compass for light-triggered DDS for biomedical applications. Thisrapidly advancing field is poised to generate breakthroughs for disease diagnosis and treatment.
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