A Red Light‐Triggered Drug Release System Based on One‐Photon Upconversion‐Like Photolysis

Abstract

Photoresponsive drug release systems can enhance drug accumulation at the sites where light is applied. Nowadays, the photocleavable groups used in the systems usually require ultraviolet or blue light irradiation, which limits tissue penetration depth and is harmful to normal cells and living bodies. A one-photon upconversion-like photolysis strategy, which can cleave green light-activatable prodrugs with red light at the presence of a red light-excitable photosensitizer in organic solvents, is developed. However, both the prodrug and photosensitizer are hydrophobic and their energy transfer process is sensitive to oxygen molecules. Here, a simple strategy to address these problems by loading the two components in biocompatible and biodegradable polymeric micelles, is presented. The developed low-irradiance red light-triggered drug release system has a size around 40 nm and exhibits good stability in aqueous solutions. The micellar encapsulation protects the photolysis reaction from oxygen quenching in normoxia aqueous solutions. The therapeutic effect of the system enhanced by the redlight irradiation is demonstrated through in vitro and in vivo studies, indicating promising potential in cancer therapy. The study provides the first example and also an important reference for applying one-photon upconversion-like photolysis in biomedical applications.

Photoresponsive prodrug‐dye nanoassembly for in‐situ monitorable cancer therapy

“…The result can be explained by the fact that some byproducts were generated during the photocleavage reaction and the released Cb was not stable in aqueous solutions (Figure S6). 20,34,37 These results demonstrated that IR783/BC NPs exhibited both good stability in the dark and excellent photocleavable ability upon light irradiation, confirming their potency for photoresponsive drug delivery.…”

“…Recently, photoresponsive prodrugs have been developed with tailor‐made structures containing photocleavable moieties such as coumarin and boron‐dipyrromethene (BODIPY) for photoactivable chemotherapy 17–19 . For instance, BODIPY‐chlorambucil (BC) prodrug, of which the BODIPY group can be efficiently cleaved upon light irradiation, was developed and achieved effective antitumor effect with the utilization of laser light 20 . However, due to the hydrophobicity of most photocleavable groups, water solubility of the reported photoresponsive prodrugs is generally poor, which hindered their utility in vivo 21,22 …”

Green Light‐Triggered Intraocular Drug Release for Intravenous Chemotherapy of Retinoblastoma

“…[ 9 , 10 ] Among the various strategies, light activation has demonstrated to be a promising option, by which the release of bioactive molecules can be readily controlled with high spatiotemporal precision. [ 11 , 12 , 13 , 14 , 15 ] Nevertheless, the currently used photocleavable groups in such systems usually require ultraviolet (UV) or blue light irradiation, which exhibited potential light‐induced toxicity and low penetrating ability. [ 16 ] Compared with other tissues, the transparent vitreous body can be efficiently penetrated by light, which provides excellent potentials for light‐triggered drug delivery systems in the treatment of eye diseases.…”

One-photon red light-triggered disassembly of small-molecule nanoparticles for drug delivery

“…Such process requires oxygen-free environment to maximize the photolysis efficiency because oxygen can hinder TTET by quenching the excited triplet states of prodrug or photosensitizer. A further study on a polymeric PLA-PEG nanocarrier encapsulating prodrug and photosensitizer enabled red light-triggered prodrug photolysis in normoxia conditions [ 21 ]. However, the type of drugs that can be used in the system is limited, since the synthesis of light-responsive prodrugs requires the drugs to contain certain functional groups (e.g., carboxyl group).…”