Cancer-mitochondria-targeted photodynamic therapy with supramolecular assembly of HA and a water soluble NIR cyanine dye

Thomas, Ajesh P.; Palanikumar, L.; Jeena, M. T.; Kim, Kibeom; Ryu, Ja‐Hyoung

doi:10.1039/c7sc03169f

Cited by 146 publications

(99 citation statements)

References 38 publications

(12 reference statements)

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“…This system was highly tumor-selective, due to the overexpression of the cell surface CD44 as the HA receptor. The near-infrared light was used to activate the PS, resulting in an effective PDT killing effect with an EC 50 value of 5-7 µM against HeLa and MDA-MB-231 cell lines [38].…”

Section: Mitochondrial Targeted Ps In Drug Delivery Systemmentioning

confidence: 99%

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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There have been many reports on the relationship between mitochondrial oxidative stress and various types of diseases. This review covers mitochondrial targeting photodynamic therapy and photothermal therapy as a therapeutic strategy for inducing mitochondrial oxidative stress. We also discuss other mitochondrial targeting phototherapeutic methods. In addition, we discuss anti-oxidant therapy by a mitochondrial drug delivery system (DDS) as a therapeutic strategy for suppressing oxidative stress. We also describe cell therapy for reducing oxidative stress in mitochondria. Finally, we discuss the possibilities and problems associated with clinical applications of mitochondrial DDS to regulate mitochondrial oxidative stress.Biomolecules 2020, 10, 83 2 of 23 Parkinson's and Alzheimer's diseases, by the direct neutralization of ROS and by suppressing inflammation [5,6]. Furthermore, CoQ 10 , a potent ubiquinone antioxidant, has been reported to show significant protective effects on mitochondria of the pancreatic beta cells during the oxidative stress induced by the chronic use of tacrolimus [7]. Due to the highly hydrophobic characteristics and the fact that most of the antioxidant molecules accumulate in a nonspecific manner, a high dose is needed to obtain the desired effects. Thus, the selective delivery of this compound would be expected to further strengthen its effectivity.In the context of cancer therapy, mitochondrial ROS were found to play an important role as a signaling molecule in controlling cell proliferation by virtue of its ability to regulate the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway [8]. Moreover, antioxidant activity, such as GSH and thioredoxin, was also reported to be essential for the initiation of and the progression of cancer. Inhibition of the antioxidant activity resulted in a significant reduction in tumor progression and metastasis [9][10][11]. These findings suggest that cancer cells are maintained under conditions of ROS stress and that antioxidant supplementation may be irrelevant for cancer therapy [12][13][14]. However, ROS interact with several major biologically active molecules such as proteins, lipids, and nucleic acids, leading to irreversible oxidative damage and the further induction of lethal effects for the cells. Therefore, promoting ROS production could be a promising strategy for treating tumors. There are numerous methods that can be employed to promote ROS levels in cancers, i.e., depleting or inhibiting antioxidant activity [15,16] and inhibiting the mitochondrial respiratory system [17], and producing an excessive amount of ROS through photochemical reactions. The latter effort shows a high selectivity for tumor cells, making it more encouraging in contrast to other efforts.This review focuses on therapeutic strategies for regulating mitochondrial oxidative stress. The main theme includes therapeutic strategies designed to induce oxidative stress and suppress mitochondrial oxidative stress (Figure 1). As ...

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Section: Mitochondrial Targeted Ps In Drug Delivery Systemmentioning

confidence: 99%

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

et al. 2020

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“…Next, to reveal the intracellular 1 O 2 levels generated by FUCP-1, Singlet Oxygen Sensor Green (SOSG) was used as the 1 O 2 capture agent. 53,54 As shown in Fig. S11, † no obvious uorescence was observed in the groups NRh-1 with and without laser.…”

Section: O 2 Photosensitizing Ability Of Fucp-1mentioning

confidence: 81%

Development of a novel anti-tumor theranostic platform: a near-infrared molecular upconversion sensitizer for deep-seated cancer photodynamic therapy

Tian

Sun

et al. 2019

Chem. Sci.

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“…The HA-IR-Pyr aggregates showed an IC 50 of 5-7 µM in HeLa and MDA-MB 231 cell lines under PDT conditions (808 nm laser, 3 min irradiation, 200 mW), and no activity toward normal cells. In vivo administration of HA-IR-Pyr followed by laser irradiation also showed significant tumor reduction, which renders it a good candidate for mitochondrial-targeted PDT with high water solubility [65]. The same group developed another powerful photodynamic therapeutic agent with a synergistic effect.…”

Section: Mitochondria-targeted Small Molecules For Pdtmentioning

confidence: 99%

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

Jeena

Kim

Jin

et al. 2019

Cancers

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The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches.In healthy cells, mitochondria execute a controlled regulation of multiple functions to maintain the cellular growth-death cycle. However, in the case of tumor cells, to meet the higher metabolic demand of rapidly proliferating cells, dysregulation of mitochondrial metabolism occurs [14,15]. The difference between cancer cell mitochondria and normal cells includes several functional alterations, such as mutation of mtDNA that lead to OXPHOS (oxidative phosphorylation) inhibition and thus deficient respiration and ATP generation, mutation of mtDNA-encoded mitochondrial enzymes, such as SDH (succinate dehydrogenase), IDH1 (isocitrate dehydrogenase 1), IDH2 (isocitrate dehydrogenase 2) [16], and structural differences, such as higher membrane potential of cancer cell mitochondria and higher basicity inside the mitochondrial lumen. The evasion of cell death or inhibition of mitochondria-mediated apoptosis is a hallmark for cancer. Mitochondria generate ROS, which is necessary for signaling under normal conditions. However, when apoptosis is inhibited in the case of cancer, ROS contributes to the neoplastic transformation. Furthermore, for supporting tumor cell survival under harsh tumorigenic conditions, such as nutrient depletion and hypoxia, mitochondria provide flexibility in several pathways either by up-or downregulation [17]. This altered mitochondrial metabolism of cancer cells compared with that of their normal counterparts is advantageous for the selective targeting of cancer mitochondria in therapeutics, which focuses on the cancer mitochondria specific features [18]. Directing the therapeutic agent to the mitochondria is an efficient way of eliminating cancer cells because the designed drug molecules could act at the central point of the cell, and therefore, engineering mitochondrial-targeted therapeutic agents have gained much interest in cancer thera...

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Cancer-mitochondria-targeted photodynamic therapy with supramolecular assembly of HA and a water soluble NIR cyanine dye

Abstract: Herein, we introduce an indocyanine derivative (IR-Pyr) that is highly water soluble, exhibiting higher mitochondrial targetability and better photostability than IR-780.

Cited by 146 publications

References 38 publications

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress

Development of a novel anti-tumor theranostic platform: a near-infrared molecular upconversion sensitizer for deep-seated cancer photodynamic therapy

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

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