Cationic telluroviologen derivatives as type‐I photosensitizers for tumor photodynamic theranostics

Abstract

The hypoxia of the tumor microenvironment (TME) seriously restricts the photodynamic therapy (PDT) effect of conventional type-II photosensitizers, which are highly dependent on O 2 . In this work, a new type-I photosensitizer (TPE-TeV-PPh 3 ) consisting of a tetraphenylethylene group (TPE) as a bioimaging moiety, triphenyl-phosphine (PPh 3 ) as a mitochondria-targeting group, and telluroviologen (TeV 2+ ) as a reactive oxygen species (O 2•− , •OH) generating moiety is developed. The luminescence intensity of TPE-TeV-PPh 3 increased significantly after specific oxidation by excess H 2 O 2 in the TME without responding to normal tissues via the formation of Te═O bond, which can be used for monitoring abnormal H 2 O 2 , positioning, and imaging of tumors. TPE-TeV-PPh 3 with highly reactive radicals generation and stronger hypoxia tolerance realizes efficient cancer cell killing under hypoxic conditions, achieving 88% tumor growth inhibition. Therefore, TPE-TeV-PPh 3 with low phototoxicity in normal tissue achieves tumor imaging and effective PDT toward solid tumors in response to high concentrations of H 2 O 2 in the TME, which provides a new strategy for the development of type-I photosensitizers. K E Y W O R D S photodynamic anti-cancer therapy, telluroviologen, tumor imaging, type-I photosensitizer INTRODUCTIONCancer is a major threat to human health and development. [1] Traditional cancer therapies, including surgery, chemotherapy, and radiotherapy, have been used clinically for decades, but they have inherent shortcomings. For example, surgery requires chemotherapy and radiotherapy for adjuvant treatment after tumor removal to prevent recurrence and deterioration. [2] However, radiotherapy and chemotherapy are always accompanied by serious side effects and resistance during treatment. [3] Compared with traditional therapy methods, photodynamic therapy (PDT) has received increasing attention due to its low systemic toxicity, high selectivity, and reduced trauma without drug/radiation resistance. [4] The main mechanism of action is to employ a light source to excite the photosensitizer to produce reactive oxygen Qi Sun and Qi Su contributed equally to this work.

Oxidization enhances type I ROS generation of AIE-active zwitterionic photosensitizers for photodynamic killing of drug-resistant bacteria

“…[26][27][28][29] AIE-active PSs usually exhibit strong emission and an aggregationinduced ROS generation effect and thus provide new opportunities for the development of PDT. 30,31 Recently, although several AIE-active type I PSs have been developed, [32][33][34] there are few reports on how to improve the ROS production efficacy of type I PSs.…”

Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise Therapy of Bacterial Infections

“…Since the surface of bacteria is negatively charged, one of the most commonly used strategies to improve bacteria selectivity is to use cationic photosensitizers. − For example, cationic phenothiazinium dyes have been widely used in the clinical treatment of dental infections taking advantage of the high electrostatic interaction with bacteria . Except for electrostatic interaction, the metabolic incorporation of photosensitizers in the biosynthetic pathway of peptidoglycan − is also an effective strategy to improve the selectivity of photosensitizers to different bacteria without affecting mammalian cells. , After modifying photosensitizers with peptidoglycan building blocks, such as d -amino acids − and N -acetyl muramic acid, the photosensitizers could selectively label bacteria through the biosynthetic pathway of peptidoglycan and undergo APDT.…”

Multifunctional nanomicelles constructed by aggregation and de-aggregation strategy for magnetic resonance/NIR II fluorescence imaging guided Type I photodynamic therapy

“…Among the AIE PSs, the ones that mostly generate Type I ROS (H2O2, O2• -, •OH, etc. ), have attracted tremendous attentions owing to the stronger hypoxia tolerance than traditional PSs that mainly generate Type II ROS ( 1 O2) [20][21][22][23], which are the excellent alternative material for PDT [24]. Therefore, conjugating AIEgens with GBCA to form AIE-Gd probes would be an ideal candidate to construct dual-modal imaging and therapeutic agents.…”