Self-Monitoring the Endo-Lysosomal Escape and Near-Infrared-Activated Mitophagy To Guide Synergistic Type-I Photodynamic and Photothermal Therapy

Abstract

Considering the multiple biological barriers before the entry of photosensitizers (PSs) into cytoplasm, it is of paramount importance to track PSs to elucidate their behaviors and distributions to guide the photodynamic therapy (PDT). Also, the developed PSs suffer from strong oxygen dependency. However, reports on such ideal theranostic platforms are rare. Herein, we developed a theranostic platform (CMTP-2) based on the coumarin-based D-π-A system, which, for the first time, can reveal the holistic intracellular delivery pathway and near-infrared (NIR)-activated mitophagy to guide synergistic type-I PDT and photothermal therapy. The dynamic endo-lysosomal escape of CMTP-2 was monitored, as well as its changeable distributions in endosomes, lysosomes, and mitochondria, demonstrating the preferential accumulation in mitochondria at the end. Upon NIR-I irradiation, CMTP-2 generated toxic radicals and heat, triggering the execution of mitophagy and apoptosis. In vivo experiments on mice indicated that CMTP-2 under 808 nm irradiation realized complete cancer ablation, showing great potential for advancements in synergistic phototherapy.

Emergence of Surface-Enhanced Raman Scattering Probes in Near-Infrared Windows for Biosensing and Bioimaging

“…PDT therapy is an emerging therapy that uses photosensitizers to absorb radiant energy. Accompanied by biological effects with the participation of oxygen molecules, highly active singlet oxygen ( 1 O 2 ) can oxidize with nearby biological macromolecules to produce cytotoxicity and kill cells in the exposed area. , However, due to many technical difficulties, PDT has not been widely used as a general therapy in clinical practice. A major challenge is the poor solubility of the photosensitizer (PS), which limits the application in vivo .…”

A GLUTs/GSH cascade targeting-responsive bioprobe for the detection of circulating tumor cells

“…After endocytosis, GluCC could achieve lysosome escape due to the proton sponge effect caused by the acid-responsive motif N,N-diethylamino in GluCC. 22 Furthermore, the GSH responsiveness of GluCC in cancer cells was verified. As shown in Fig.…”

Molecular Tailoring Based on Forster Resonance Energy Transfer for Initiating Two-Photon Theranostics with Amplified Reactive Oxygen Species

“…In our previous work, the CC bond or thiophene group was usually added for enhancing the intramolecular charge transfer (ICT) to make the absorbance of PSs shift to the near-infrared (NIR) region and reduce the energy gap between the singlet and triplet states (Δ E ST ) through the prolonging π-conjugate (Scheme ). , Nevertheless, these derivatives are highly conjugated with poor biocompatibility and antibleaching properties under NIR light. Hence, a straightforward manner is urgently needed to develop PSs with enhanced PDT in the NIR window.…”