Ultralow-intensity NIR light triggered on-demand drug release by employing highly emissive UCNP and photocleavable linker with low bond dissociation energy

Background: The design of novel nanoparticles with higher therapeutic efficacy and lower side effects, is still difficult but encouraging in cancer therapy. Specifically, for upconversion nanoparticles (UCNP)-based drug release, a high intensity of NIR light (1.4~5.0 W/cm(2)) above the maximum permissible exposure (0.33 W/cm(2) for 980 nm) is commonly used and severely limits its practical application. Methods: The highly emissive UCNP is first synthesized and then coated with mesoporous silica (MS) shell (UCMS). Next, the surface of UCMS is modified with the thioether (-S-BP) linker, leading to UCMS-S-BP nanoparticles. Finally, after the drug doxorubicin (Dox) is loaded into the pore channels of UCMS, the pore openings are blocked by the β-cyclodextrin (β-CD) gatekeeper through the association with the -S-BP linker (UCMS(Dox)-S-BP@β-CD). Results: Upon 980 nm NIR light irradiation with an ultralow intensity of 0.30 W/cm(2), it is found that the loaded Dox can be released through the cleavage of thioether linkers triggering dissociation of β-CD gatekeepers. The in vitro results exhibited significantly therapeutic efficacy with 85.2% of HeLa cells killed in this study. Conclusions: An ultralow-intensity NIR light triggered on-demand drug release system has been developed by employing highly emissive UCNP and photocleavable linker with low bond dissociation energy to avoid the potential photodamage on healthy neighbor cells.