Application of near-infrared-activated and ATP-responsive trifunctional upconversion nano-jelly for in vivo tumor imaging and synergistic therapy

Upconversion nanoparticles (UCNPs)-mediated in-situ imaging and synergistic therapy may be an effective approach against tumors. However, it remains a challenge to improve therapeutic index and reduce toxicity. Here, we investigated the construction process of a three-layer (core-shell-shell) upconversion nano-jelly hydrogels (UCNJs) coated with stimulus-responsive deoxyribonucleic acid chains, aiming to achieve selective recognition of tumor cells and controlled release of drugs. The UCNJs have a NaYF4: Yb, Er core with an outer silica shell with embedded methylene blue (MB). Then the outer layer was coated with mesoporous silica and loaded with doxorubicin (DOX). Finally, polyacrylamide chains containing anti-adenosine triphosphate (ATP) aptamer sequences were assembled layer-by-layer on the surface of particles to form DNA hydrogels to lock DOX. Under near-infrared irradiation, green light (540 nm) emitted by UCNJs can be used for imaging, while red light (660 nm) is absorbed by MB. The latter generates singlet oxygen, resulting in photodynamic therapy (PDT) effect to inhibit tumor growth. UCNJs also can recognize ATP in tumor cells, leading to hydrogel degradation and DOX release. The hydrogel coating can increase drug-carrying capacity of mesoporous materials and improve biocompatibility. Therefore, the UCNJs has great potential advantages for application in the field of cancer diagnosis and treatment.