A mitochondrion-targeting Mn(ii)-terpyridine complex for two-photon photodynamic therapy

Abstract

<p>A mitochondrion-targeting Mn^II-terpyridine complex (MTP) has been developed for providing a good spatial condition to generate ¹O₂, which further promoted the two-photon photodynamic therapy (PDT) effect.</p>

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy

“…Other. Li et al reported mitochondria-targeted Mn(II)−terpydidine complexes (497) for enhanced intracellular oxygen and two-photon-excited PDT efficiency (Figure 239), 1075 in which the D−A configuration of terpydidine ligand was introduced for enhanced two-photon absorption of 497 (σ 2 = 165 GM) and protonation of aniline acts as a mitochondria targeting of Mn(II) complex with a Pearson correlation coefficient of 0.81. Interestingly, the Mn(II) center catalyzed H 2 O 2 -mediated generation of • OH and oxygen via Fenton-like conversion, which enhanced the PDT efficiency.…”

Mito‐Bomb: Targeting Mitochondria for Cancer Therapy

“…PDT 1) Noninvasiveness 2) Accurate controllability 3) Low systemic toxicity 4) Minimal drug resistance 5) Limited side effects 1) Limited damage scope due to the short diffusion distance (<0.02 µm) and the lifetime (<0.04 µs) of ROS 2) Low penetration depth of the light source which cannot effectively cure deep tumors 3) Reduced ROS generation and high skin phototoxicity of traditional PSs due to the rigid plane and the inherent hydrophobic structure 4) Hypoxic environment of TME limits the effective treatment of PDT 5) Difficult to treat disseminated, metastatic tumors [33,306,307,370,371] PTT 1) Noninvasiveness 2) Temporal and spatial selectivity 3) Extremely low damage to surrounding healthy tissues 4) No local O 2 required 5) Minimal side effects 1) Non-biodegradable, immunogenic, poor pharmacokinetics, or potential for long-term toxicity of most photothermal agents 2) Low thermal stability during prolonged laser irradiation 3) Less absorbed in cells and tissues 4) Residual cells may rapidly develop heat resistance, leading to tumor recurrence 5) Difficult to treat disseminated, metastatic tumors 6) High skin phototoxicity due to laser power is higher than skin tolerance [51,55,224,229,[372][373][374][375][376]] Gas therapy Mitochondria are the distal target of CO which might better achieve the ideal therapeutic effect 1) Risk of CO poisoning attributing to the lack of ability to target tumors 2) Uncontrollability of CO ingestion [60,368] RT-RDT Low dosage of deeply penetrating X-rays Large skin injury [66] CT 1) High effectiveness of tumor treatment 2) Treat metastatic tumor 1) Inevitable multidrug resistance 2) High nonspecific toxicity of normal tissues and blood 3) Low targeting selectivity to malignant tissues 4) Great harm to body and mind of patients 5) Hypoxia limits therapeutic efficiency 6) Damage the immune system 7) Increase incidence of second cancers [59,60,73,80] Combination PDT& PTT 1) Minimize multi-drug resistance 2) The therapeutic efficiency of cancer is amplified by "killing two birds with one stone." For example, the phototherapy agents IR780 and ICG can be used as PS and photothermal agent to treat PDT and PTT simultaneously 3) Low risk of recurrence 1) Complex molecular design and time-consuming and expensive chemical synthesis and purification 2) Poor biodegradability and potential long-term toxicity 3) Lack of phototherapeutic agents with maximum absorption above 800 nm [52,…”

Metal‐Coordinated Supramolecular Self‐Assemblies for Cancer Theranostics

“…[ 32 , 115 ] For example, Yang and coworker constructed a mitochondrial targeting Mn 2+ ‐terpyridine (MTP) complex for two‐photon PDT by chelating terpyridine derivates with Mn 2+ ; the Mn 2+ center within MTP catalyzed the conversion of H 2 O 2 in malignant cancer cells into O 2 and ROS, which improved the PDT effect during in vivo experiments. [ 116 ]…”

“…[32,115] For example, Yang and coworker constructed a mitochondrial targeting Mn 2+ -terpyridine (MTP) complex for two-photon PDT by chelating terpyridine derivates with Mn 2+ ; the Mn 2+ center within MTP catalyzed the conversion of H 2 O 2 in malignant cancer cells into O 2 and ROS, which improved the PDT effect during in vivo experiments. [116] In a recent report, Zhao and coworkers constructed an antitumor nanomedicine for PDT via multicomponent self-assembly, in which Prussian blue analogs served as the parent materials. [33] The self-assembly of Mn 2+ ions, photosensitizers, and organic ligands was achieved based on the coordination bond, and the well-defined GSH-depletion nanodrugs was finally protected with biocompatible polyvinylpyrrolidone (PVP).…”