Upconversion Nanoparticle-Induced Multimode Photodynamic Therapy Based on a Metal-Organic Framework/Titanium Dioxide Nanocomposite.

Photodynamic therapy (PDT) possesses two pathways depending on the type of high-toxicity reactive oxygen species (ROS), superoxide anion radical (O2·-) and hydroxyl radical (·OH) generated through Type I and singlet oxygen (1O2) generated through Type II, inducing cancer cell apoptosis. However, the low efficiency of ROS generation and poor biocompatibility are the limitations of the traditional photosensitizers for PDT. Herein, inspired by photochemical reactions of titanium dioxide and porphyrin-based metal-organic frameworks, we developed a nanoplatform by covering ultrasmall titanium dioxide nanoparticles on a heterodimer made up of upconversion nanoparticles and metal-organic frameworks, realizing a multimode PDT through Type I and Type II mechanisms. Once irradiated by a near-infrared light, upconversion nanoparticles could generate ultraviolet and visible lights, which were not only able to stimulate different photochemical reactions of titanium dioxide and porphyrin but also accomplish deep penetration photodynamic therapy. Our photosensitive agent exhibited good biocompatibility and an effective multimode PDT performance, which could meet the needs of different situations of photodynamic therapy in the future.

Cancer Cell Membrane Camouflaged Nanoprobe for Catalytic Ratiometric Photoacoustic Imaging of MicroRNA in Living Mice.

Herein, a cancer cell (MCF-7 cell) membrane-encapsulated dendritic mesoporous silica nanoparticle simultaneously functionalized with DNA-photoacoustic (DNA-PA) probes and glutathione (GSH)-responsive DNA fuel strands for PA imaging of tumor-related miRNA in living mice with signal amplification ability is developed. It is demonstrated that one target miRNA can trigger disassembly of multiple PA fluorophore probes from the quencher with the aid of GSH-responsive DNA fuel strands via the entropy-driven process, resulting remarkable amplified change of PA signal ratio. Using oncogenic miRNA-21 as a model, a linear relationship between miRNA-21 concentrations and PA ratio in a dynamic range from 10 × 10-12 m to 100 × 10-9 m and a limit of detection down to 11.69 × 10-12 m are established. The accurate PA signal observation related to miRNA-21s in the tumor area in living mice is demonstrated, and the PA signal ratio increases significantly via the injection of miRNA-21. It is anticipated that the catalytic ratiometric PA imaging system can be applied to an array of molecular detection in living system by rational detection probe design.

A Bacteriochlorin-Based Metal-Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging-Guided Highly Efficient Photodynamic Therapy.

Hypoxic tumor microenvironment is the bottleneck of the conventional photodynamic therapy (PDT) and significantly weakens the overall therapeutic efficiency. Herein, versatile metal-organic framework (MOF) nanosheets (DBBC-UiO) comprised of bacteriochlorin ligand and Hf6(µ3-O)4(µ3-OH)4 clusters to address this tricky issue are designed. The resulting DBBC-UiO enables numerous superoxide anion radical (O2 -•) generation via a type I mechanism with a 750 nm NIR-laser irradiation, part of which transforms to high toxic hydroxyl radical (OH•) and oxygen (O2) through superoxide dismutase (SOD)-mediated catalytic reactions under severe hypoxic microenvironment (2% O2), and the partial recycled O2 enhances O2 -• generation. Owing to the synergistic radicals, it realizes advanced antitumor performance with 91% cell mortality against cancer cells in vitro, and highly efficient hypoxic solid tumor ablation in vivo. It also accomplishes photoacoustic imaging (PAI) for cancer diagnosis. This DBBC-UiO, taking advantage of superb penetration depth of the 750 nm laser and distinct antihypoxia activities, offers new opportunities for PDT against clinically hypoxic cancer.