scholarly journals Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiexin Wen ◽  
Yong Luo ◽  
Hui Gao ◽  
Liang Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Oxygen Consumption ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Mitochondrial Respiratory Chain ◽  
Therapeutic Modality ◽  
Promising Alternative ◽  
Atp Production ◽  
Consumption Reduction ◽  
Supply Reduction

Abstract Background Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. Results The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusions This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment. Graphical Abstract

scholarly journals Mitochondria-Targeted Nanoplatforms For Enhanced Photodynamic Therapy Against Hypoxia Tumor

2021 ◽  
Author(s):  
Jiexin Wen ◽  
Yong Luo ◽  
Hui Gao ◽  
Liang Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Oxygen Consumption ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Mitochondrial Respiratory Chain ◽  
Therapeutic Modality ◽  
Promising Alternative ◽  
Atp Production ◽  
Consumption Reduction ◽  
Supply Reduction

Abstract Background: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers.Results: The as-synthesized nanoplatforms penetrated deeply into the interior regions of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment.Conclusions: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Visible Light ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Molecular Oxygen ◽  
Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Visible Light ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Molecular Oxygen ◽  
Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

scholarly journals Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells Lacking COQ6

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Manuel J. Acosta Lopez ◽  
Eva Trevisson ◽  
Marcella Canton ◽  
Luis Vazquez-Fonseca ◽  
Valeria Morbidoni ◽  
...  
Keyword(s):  
Vanillic Acid ◽  
Coenzyme Q ◽  
Mitochondrial Respiratory Chain ◽  
Human Cell Line ◽  
Food Additive ◽  
Large Set ◽  
Promising Alternative ◽  
Atp Production ◽  
Redox Active ◽  
Genes Encoding

Coenzyme Q (CoQ), a redox-active lipid, is comprised of a quinone group and a polyisoprenoid tail. It is an electron carrier in the mitochondrial respiratory chain, a cofactor of other mitochondrial dehydrogenases, and an essential antioxidant. CoQ requires a large set of enzymes for its biosynthesis; mutations in genes encoding these proteins cause primary CoQ deficiency, a clinically and genetically heterogeneous group of diseases. Patients with CoQ deficiency often respond to oral CoQ10 supplementation. Treatment is however problematic because of the low bioavailability of CoQ10 and the poor tissue delivery. In recent years, bypass therapy using analogues of the precursor of the aromatic ring of CoQ has been proposed as a promising alternative. We have previously shown using a yeast model that vanillic acid (VA) can bypass mutations of COQ6, a monooxygenase required for the hydroxylation of the C5 carbon of the ring. In this work, we have generated a human cell line lacking functional COQ6 using CRISPR/Cas9 technology. We show that these cells cannot synthesize CoQ and display severe ATP deficiency. Treatment with VA can recover CoQ biosynthesis and ATP production. Moreover, these cells display increased ROS production, which is only partially corrected by exogenous CoQ, while VA restores ROS to normal levels. Furthermore, we show that these cells accumulate 3-decaprenyl-1,4-benzoquinone, suggesting that in mammals, the decarboxylation and C1 hydroxylation reactions occur before or independently of the C5 hydroxylation. Finally, we show that COQ6 isoform c (transcript NM_182480) does not encode an active enzyme. VA can be produced in the liver by the oxidation of vanillin, a nontoxic compound commonly used as a food additive, and crosses the blood-brain barrier. These characteristics make it a promising compound for the treatment of patients with CoQ deficiency due to COQ6 mutations.

scholarly journals Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Visible Light ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Molecular Oxygen ◽  
Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

Targeted nanocarriers based on iodinated-cyanine dyes as immunomodulators for synergistic phototherapy

Nanoscale ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 11008-11025 ◽  
Author(s):  
Jinnan Chi ◽  
Qingming Ma ◽  
Zijun Shen ◽  
Caiyun Ma ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Cyanine Dyes ◽  
Therapeutic Strategies ◽  
Local Tumor

Photodynamic therapy (PDT), as one of the most powerful photo-therapeutic strategies for cancer treatment with minimum invasiveness, can effectively damage local tumor cells and significantly induce systemic antitumor immunity.

scholarly journals Autophagy Regulation and Photodynamic Therapy: Insights to Improve Outcomes of Cancer Treatment

2021 ◽  
Vol 10 ◽  
Author(s):  
Waleska K. Martins ◽  
Renata Belotto ◽  
Maryana N. Silva ◽  
Daniel Grasso ◽  
Maynne D. Suriani ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Light Sources ◽  
Regulated Cell Death ◽  
Age Related ◽  
Cell Death Mechanisms

Cancer is considered an age-related disease that, over the next 10 years, will become the most prevalent health problem worldwide. Although cancer therapy has remarkably improved in the last few decades, novel treatment concepts are needed to defeat this disease. Photodynamic Therapy (PDT) signalize a pathway to treat and manage several types of cancer. Over the past three decades, new light sources and photosensitizers (PS) have been developed to be applied in PDT. Nevertheless, there is a lack of knowledge to explain the main biochemical routes needed to trigger regulated cell death mechanisms, affecting, considerably, the scope of the PDT. Although autophagy modulation is being raised as an interesting strategy to be used in cancer therapy, the main aspects referring to the autophagy role over cell succumbing PDT-photoinduced damage remain elusive. Several reports emphasize cytoprotective autophagy, as an ultimate attempt of cells to cope with the photo-induced stress and to survive. Moreover, other underlying molecular mechanisms that evoke PDT-resistance of tumor cells were considered. We reviewed the paradigm about the PDT-regulated cell death mechanisms that involve autophagic impairment or boosted activation. To comprise the autophagy-targeted PDT-protocols to treat cancer, it was underlined those that alleviate or intensify PDT-resistance of tumor cells. Thereby, this review provides insights into the mechanisms by which PDT can be used to modulate autophagy and emphasizes how this field represents a promising therapeutic strategy for cancer treatment.

Role of Exosomes in Photodynamic Anticancer Therapy

2020 ◽  
Vol 27 (40) ◽  
pp. 6815-6824 ◽  
Author(s):  
Yuan Jiang ◽  
Chuanshan Xu ◽  
Wingnang Leung ◽  
Mei Lin ◽  
Xiaowen Cai ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Basic Principle ◽  
Photochemical Reaction ◽  
Cell Communication ◽  
Anticancer Therapy ◽  
Bioactive Molecules ◽  
Promising Alternative ◽  
Tumor Tissues ◽  
Significant Attention

Photodynamic Therapy (PDT) is a promising alternative treatment for malignancies based on photochemical reaction induced by Photosensitizers (PS) under light irradiation. Recent studies show that PDT caused the abundant release of exosomes from tumor tissues. It is well-known that exosomes as carriers play an important role in cell-cell communication through transporting many kinds of bioactive molecules (e.g. lipids, proteins, mRNA, miRNA and lncRNA). Therefore, to explore the role of exosomes in photodynamic anticancer therapy has been attracting significant attention. In the present paper, we will briefly introduce the basic principle of PDT and exosomes, and focus on discussing the role of exosomes in photodynamic anticancer therapy, to further enrich and boost the development of PDT.

Nanocarriers for Photodynamic Therapy Intended to Cutaneous Tumors

2021 ◽  
Vol 22 ◽  
Author(s):  
Maria Bernadete Riemma Pierre
Keyword(s):  
Photodynamic Therapy ◽  
Drug Delivery Systems ◽  
Active Agent ◽  
Therapeutic Modality ◽  
Tissue Penetration ◽  
Promising Tool ◽  
Skin Cancers ◽  
Superficial Basal Cell Carcinoma ◽  
The Stability ◽  
Disor Ders

Abstract: Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant skin disor-ders, including Bowen's disease skin cancers and Superficial Basal Cell Carcinoma (BCC). Several photosensitizers (PSs) have been explored for tumor destruction of skin cancers, after their activation by a light source of appropriate wavelength. Topical release of PSs avoids prolonged photosensitization reactions associated with systemic administration; however, its clinical usefulness is influenced by its poor tissue penetration and the stability of the active agent. Nanotechnology-based drug delivery systems are promising tool to enhance the efficiency for PDT of cancer. This review focuses on PSs encap-sulated in nanocarriers explored for PDT of skin tumors.

Anticancer Activity of Diosgenin and its Semi-synthetic Derivatives: Role in Autophagy Mediated Cell Death and Induction of Apoptosis

2021 ◽  
Vol 21 ◽  
Author(s):  
Nivedita Bhardwaj ◽  
Nancy Tripathi ◽  
Bharat Goel ◽  
Shreyans K. Jain
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Rational Approach ◽  
Potential Candidate ◽  
Potential Implication ◽  
Apoptosis Protein ◽  
Synthetic Derivatives

: During cancer progression, the unrestricted proliferation of cells is supported by the impaired cell death response provoked by certain oncogenes. Both autophagy and apoptosis are the signaling pathways of cell death, which are targeted for cancer treatment. Defects in apoptosis result in reduced cell death and ultimately tumor progression. The tumor cells lacking apoptosis phenomena are killed by ROS- mediated autophagy. The autophagic programmed cell death requires apoptosis protein for inhibiting tumor growth; thus, the interconnection between these two pathways determines the fate of a cell. The cross-regulation of autophagy and apoptosis is an important aspect to modulate autophagy, apoptosis and to sensibilise apoptosis-resistant tumor cells under metabolic stress and might be a rational approach for drug designing strategy for the treatment of cancer. Numerous proteins involved in autophagy have been investigated as the druggable target for anticancer therapy. Several compounds of natural origin have been reported, to control autophagy activity through the PI3K/Akt/mTOR key pathway. Diosgenin, a steroidal sapogenin has emerged as a potential candidate for cancer treatment. It induces ROS-mediated autophagy, inhibits PI3K/Akt/mTOR pathway, and produces cytotoxicity selectively in cancer cells. This review aims to focus on optimal strategies using diosgenin to induce apoptosis by modulating the pathways involved in autophagy regulation and its potential implication in the treatment of various cancer. The discussion has been extended to the medicinal chemistry of semi-synthetic derivatives of diosgenin exhibiting anticancer activity.

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