Cancer‐Cell‐Activated in situ Synthesis of Mitochondria‐Targeting AIE Photosensitizer for Precise Photodynamic Therapy

Abstract

Maximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer‐cell‐specific or even cancer‐cell‐organelle‐specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo, which is difficult to achieve. Herein, we report a strategy of cancer‐cell‐activated PS synthesis, by which an efficient mitochondria‐targeting photosensitizer with aggregation‐induced‐emission (AIE) feature can be selectively synthesized as an efficient image‐guided PDT agent inside cancer cells. MOF‐199, a CuII‐based metal‐organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a CuI catalyst source for in situ click reaction to form PSs exclusively in cancer cells. The in situ synthesized PS showed mitochondria‐targeting capability, allowing potent cancer‐cell‐specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post‐treatment.

The fast-growing field of photo-driven theranostics based on aggregation-induced emission

“…257 Besides, with the loading of Cu(II)-based MOF-199, mitochondria-targeting AIE PSs could be synthesized in situ and used for precise PDT. 258 Other than simply acting as the nanocarriers of AIE PSs, different types of MOFs introduced to combine with AIE PSs can also endow them with specific functionalities, such as relieving tumor hypoxia and enhancing therapeutic efficacy. As shown in Fig.…”

Phototherapeutic anticancer strategies with first-row transition metal complexes: a critical review

“…183 We can also cite a recent work on ZnPcs that target tumours through PEG functionalization. 184 An article presented a ZnPc appended with four 2-pyridones that displays three advantages for PDT ( Zn-9 ). 185 First, Zn-9 can be excited by both 665 and 808 nm, allowing for both superficial and deep tumour treatment.…”

Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy

“…Several kinds of nanomaterials including polymeric, lipid, semiconductor, magnetic, silica, graphene oxide, and metallic nanoparticles have been used for mitochondria-targeted cancer therapies to enhance cancer cell destruction. With new mitochondria-targeting nanocarriers being developed for the delivery of PDT, PTT, and traditional chemotherapy agents [ 134 , 135 ], this is a strategy that should be applied to new cancer therapies to efficiently augment mitochondria-mediated apoptosis. As PTT and PDT methodologies become more precise, safe (targets tumor and avoids overheating of healthy tissue), and tailored to the tumor microenvironment (hypoxia and low pH), mitochondria-targeting will be an important function to implement in the delivery of these ablation agents for an augmented therapeutic effect that may be translatable for clinical application.…”