An AIE Photosensitizer with Simultaneous Type I and Type II ROS Generation: Efficient Bacterial Elimination and Hypoxic Tumor Ablation

Abstract

Aggregation induced emission (AIE) photosensitizers have attracted great attention due to their good performance in photodynamic therapy (PDT). However, the therapeutic effect of AIE photosensitizer is often highly dependent on the biological microenvironment because it is difficult to produce type I and type II reactive oxygen species (ROS) simultaneously. Herein, an electron‐rich anion‐π+ AIEgen Pys‐QM‐TT is reported, which is capable of highly generating type I and type II ROS and realizing near‐infrared fluorescence imaging synchronously. In the rational design of AIE photosensitizer, the strong electron‐donating triphenylamine unit, π‐bridge thiophene and electron‐withdrawing pyridinium salt unit can enhance the D–π–A behavior, thereby improving the intramolecular charge transfer effect and extending the wavelength. Meanwhile, the powerful D–π–A effect is supposed to reduce ∆ES‐T and promote the intersystem crossing processes, thus increasing the generation of ROS. In addition, the negatively charged anion in pyridinium salt group provides an electron‐rich environment for the excited photosensitizer, so as to promote electron transfer to generate type I ROS. Therefore, Pys‐QM‐TT can not only generate type I and type II ROS simultaneously with weak environmental dependence, but also effectively inhibit bacterial infections and ablate tumor tissue by promoting tumor cell apoptosis, inhibiting tumor cell proliferation and anti‐angiogenesis.

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer

“…Moreover, oxygen consumption will further exacerbate the hypoxia TME during MDT, thereby promoting tumor proliferation and metastasis and ultimately leading to tumor recurrence. Therefore, the catalytic generation of O 2 will help to improve MWT and promote MDT (Figure k,l). − The O 2 content of the mixed solution was first quantified using a dissolved oxygen meter to evaluate the O 2 production catalyzed by MN and MNR under MW irradiation, in which the O 2 level was essentially unchanged with the addition of H 2 O 2 to H 2 O at 25 °C, but a significant increase was detected upon subsequent addition of MN and MNR with the O 2 concentrations of 8.48 mg/L and 28 mg/L, respectively, verifying that Ru 4+ in MNR could enhance the catalytic decomposition of H 2 O 2 to produce O 2 . Thus, the MAMs of MNR could effectively deplete GSH and generate O 2 , alleviating hypoxia, disrupting the redox balance in tumor cells, and finally improving the MTDT to boost the therapeutic efficacy.…”

Dibenzothiophene-S,S-dioxide-Based Conjugated Polymers: All-in-One Two-Photon Fluorophore with ClO– Degradation for Photodynamic Anticancer Therapy

“…Photodynamic therapy (PDT) makes use of external light or laser to activate photosensitizers (PSs) and molecular oxygen to generate reactive oxygen species (ROS, e.g., singlet oxygen ( 1 O 2 ), superoxide anion radical ( • O 2 – ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical ( • OH)) to trigger noninvasive killing of cancer cells. − It is of immense advantage in terms of more precise selectivity, less drug resistance, and mitigating damage to healthy tissues and organs adjacent to tumor. − In consequence, it is prevailing with encouraging clinical efficacy against superficial skin tumors, esophageal, esophageal, bladder or lung cancer, and so forth. − PDT efficacy is positively correlated with the ROS-producing capacity of PSs, which is one of the three essential constituents in PDT (PSs, light, and oxygen). In this regard, preferable intersystem crossing (ISC) of PSs in the photosensitization process should be one of the molecular design guidelines . Since then, majority of small-molecule PSs, such as porphyrins, chlorins, methylene blue, and phthalocyanine derivatives, have been discussed.…”

“…In this regard, preferable intersystem crossing (ISC) of PSs in the photosensitization process should be one of the molecular design guidelines. 12 Since then, majority of smallmolecule PSs, such as porphyrins, 13 chlorins, 14 methylene blue, 15 and phthalocyanine derivatives, 16 have been discussed. Indeed, several porphyrin derivatives have been approvable for preclinical and clinical PDT.…”

Copper(ii)-infused porphyrin MOF: maximum scavenging GSH for enhanced photodynamic disruption of bacterial biofilm

“…15–19 The underlying principle of PDT is the activation of O 2 molecules by the irradiation of the photosensitizer (PS) with a laser of an appropriate wavelength, resulting in the production of oxidative reactive oxygen species (ROS) and the subsequent eradication of bacteria and biofilm, showing the advantages of specific space-time selectivity and minimal invasiveness. 20–22 ROS is capable of destroying bacterial cell walls, causing the leakage of cell contents and inactivating bacterial enzymes, thus resulting in irreversible bacterial death and biofilm dispersion. 23,24 Although promising, excess glutathione (GSH) in biofilm and bacteria plays a vital role in consuming ROS and severely affects PDT efficiency.…”