Photocleavage‐based Photoresponsive Drug Delivery^†

Abstract

Targeted drug delivery has been extensively studied in the last decade, whereas both passive and active targeting strategies still face many challenges, such as off-target drug release. Light-responsive drug delivery systems have been developed with high controllability and spatio-temporal resolution to improve drug efficacy and reduce off-target drug release. Photoremovable protecting groups are lightresponsive moieties that undergo irreversible photocleavage reactions upon light irradiation. They can be covalently linked to the molecule of interest to control its structure and function with light. In this review, we will summarize recent applications of photocleavage technologies in nanoparticlebased drug delivery for precise targeting and controlled drug release, with a highlight of strategies to achieve longwavelength light excitation. A greater understanding of these mechanisms and emerging studies will help design more efficient photocleavage-based nanosystems to advance photoresponsive drug delivery.

Photoremovable Protecting Groups

“…PPGs could be used in the design of more complex, nanoparticle-based drug delivery systems as well. In their structure, a PPG could be integrated in different manners to orchestrate the targeting or the drug release [62]. To address targeting, a straightforward approach is to modify directly the targeting ligands (anchored typically on the surface of the nanoparticles) with PPGs to block their interactions with their target.…”

“…Integrating the PPGs into the structure of nanocarriers, the photolysis could lead to their dissociation and the consequent release of their payload. The dissociation could be the result of various processes, as hydrophobicity change or photocleavage at the block junction of block copolymers [62]. Of the potential nanocarrier systems, photodisruption of liposomes was studied by several groups, using various photocleavable synthetic amphiphilic lipids.…”

A Photo‐degradable Crosslinker for the Development of Light‐responsive Protocell Membranes

“…[5] Photocleaving or degrading moieties are widespread in chemical synthesis and materials chemistry and are increasingly being investigated in the context of drug delivery and synthetic biology. [6] Commonly used photocleaving groups include nitroaryls, [7] arylcarbonylmethyls, [8] coumarin-4-ylmethyls, [9] as well as Ru-containing complexes. [10] Of the multitude of photoresponsive moieties available for use in light-responsive functional materials and protocells, the ortho-nitrobenzyl (o-NB) functionality has enjoyed widespread employment in a variety of chemical and living systems, including photoresponsive hydrogels and drug delivery systems, making this group ideal for use in bottom-up synthetic biology.…”

Optically Responsive Protein Coating of DNA Origami for Triggered Antigen Targeting

“…49 Light is a versatile stimuli that has previously been used for nanoparticles to induce both controlled drug release and precise targeting by photocleavage of, for instance, shielding ligands. 50 Here, we present a two-component protein coating strategy for equipping DNA origami surfaces with both targeting and camouflaging proteins. To achieve antigen targeting, we have coupled a single-chain variable antibody fragment to highly positively charged dendron structures which electrostatically bind to DNA origami.…”

“…Responsiveness could allow multiple/continuous treatment due to the addition and removal of the stimuli and, more importantly, a strict control of the stimuli’s intensity and location, which particularly applies for optical irradiation . Light is a versatile stimuli that has previously been used for nanoparticles to induce both controlled drug release and precise targeting by photocleavage of, for instance, shielding ligands …”