PH-responsive drug release and NIR-triggered singlet oxygen generation based on a multifunctional core-shell-shell structure

A multifunctional platform with pH-responsive drug release and near-infrared (NIR) light-triggered photodynamic therapy (PDT) was designed and prepared using the novel core-shell-shell structure. The multifunctional platform consists of an upconversion nanoparticle (UCNP) emission core, a photosensitizer methylene blue (MB) embedded dense silica sandwich shell, and a polyethyleneimine conjugated folic acid (PEI-FA) gated mesoporous silica (MS) outmost shell with doxorubicin hydrochloride (DOX) loaded inside. The simulated drug release experiments revealed that DOX will release from the nanoparticles because of the distortion in the PEI-FA layer under acidic conditions. Moreover, under 980 nm NIR irradiation, a 660 nm red light emission was excited, activating MB to generate a singlet oxygen (¹O₂), which acts as the PDT drug. The multifunctional platform integrated pH-responsive drug release and UCNP-based PDT drug together show promising potential in nanomedicine for future chemotherapy and NIR-triggered PDT.