A Nano Approach to Formulate Photosensitizers for Photodynamic Therapy

: Conventional treatment modalities for tumors face a variety of pitfalls including non-specific interactions leading to multiple adverse effects. These adverse effects are being overcome through innovations that are highly intense and selective delivery of therapeutic agents. More recently, Photodynamic therapy (PDT) has gained its value over conventional chemo- and radiotherapies due to the use of photosensitizers (PS) with an illuminating light source. Photosensitizers have crossed three generations with Photofrin being the first clinically approved PS for PDT. Even though these PS have proved to have cytotoxic effects against tumor cells, they suffer the selective distribution and concentration into the tumor sites that are deeply localized. To overcome these disadvantages, nanoformulations are currently being employed due to their unmatched physicochemical and surface properties. These nanoformulations include the encapsulation of PS acting as a nanocarrier for the PS or the functionalization of PS onto the surface of nanoparticles. The design of such nanoformulations involved in PDT is critical and valuable to consider. Along with PDT, several multifunctional approaches are being uplifted in the current trend where combined therapy and diagnosis are of importance. Furthermore, targeted, selective and specific delivery of the PS-loaded nanoformulations with receptor-mediated endocytosis is of interest to achieve better internalization into the tumor site. ROS generation with the interaction of PS augments cell death mechanisms exhibited due to PDT leading to the immunogenic response that further results an adaptive immune memory which prevents recurrence of tumor metastasis. Therefore, this review concentrates on the mechanisms of PDT, examples of nanocarriers and nanoparticles that are employed in PDT, combined therapies, and theranostics with PDT. A step forward, molecular mechanisms of nano-based PDT agents in killing tumor sites and design considerations for better PDT outcomes have been discussed.

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Systemic MEK inhibition enhances the efficacy of 5-aminolevulinic acid-photodynamic therapy

British Journal of Cancer ◽

10.1038/s41416-019-0586-3 ◽

2019 ◽

Vol 121 (9) ◽

pp. 758-767 ◽

Cited By ~ 6

Author(s):

Vipin Shankar Chelakkot ◽

Jayoti Som ◽

Ema Yoshioka ◽

Chantel P. Rice ◽

Suzette G. Rutihinda ◽

...

Keyword(s):

Cell Death ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Aminolevulinic Acid ◽

Combined Therapy ◽

Combined Treatment ◽

Mek Inhibitor ◽

Ros Generation ◽

Strong Basis ◽

Mek Inhibition

Abstract Background Protoporphyrin IX (PpIX) gets accumulated preferentially in 5-aminolevulinic acid (5-ALA)-treated cancer cells. Photodynamic therapy (PDT) utilises the accumulated PpIX to trigger cell death by light-induced generation of reactive oxygen species (ROS). We previously demonstrated that oncogenic Ras/MEK decreases PpIX accumulation in cancer cells. Here, we investigated whether combined therapy with a MEK inhibitor would improve 5-ALA-PDT efficacy. Methods Cancer cells and mice models of cancer were treated with 5-ALA-PDT, MEK inhibitor or both MEK inhibitor and 5-ALA-PDT, and treatment efficacies were evaluated. Results Ras/MEK negatively regulates the cellular sensitivity to 5-ALA-PDT as cancer cells pre-treated with a MEK inhibitor were killed more efficiently by 5-ALA-PDT. MEK inhibition promoted 5-ALA-PDT-induced ROS generation and programmed cell death. Furthermore, the combination of 5-ALA-PDT and a systemic MEK inhibitor significantly suppressed tumour growth compared with either monotherapy in mouse models of cancer. Remarkably, 44% of mice bearing human colon tumours showed a complete response with the combined treatment. Conclusion We demonstrate a novel strategy to promote 5-ALA-PDT efficacy by targeting a cell signalling pathway regulating its sensitivity. This preclinical study provides a strong basis for utilising MEK inhibitors, which are approved for treating cancers, to enhance 5-ALA-PDT efficacy in the clinic.

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Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review

Dermatology Research and Practice ◽

10.1155/2018/9014726 ◽

2018 ◽

Vol 2018 ◽

pp. 1-21 ◽

Cited By ~ 4

Author(s):

Taisa Rocha Navasconi Berbert ◽

Tatiane França Perles de Mello ◽

Priscila Wolf Nassif ◽

Camila Alves Mota ◽

Aline Verzignassi Silveira ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Effects ◽

Case Reports ◽

Combined Therapy ◽

Alternative Therapy ◽

Treatment Modalities ◽

Sodium Stibogluconate ◽

Mucocutaneous Leishmaniasis ◽

First Choice

The first choice drugs for the treatment of cutaneous and mucocutaneous leishmaniasis are pentavalent antimonials, sodium stibogluconate, or meglumine antimoniate. However, the treatment with these drugs is expensive, can cause serious adverse effects, and is not always effective. The combination of two drugs by different routes or the combination of an alternative therapy with systemic therapy can increase the efficacy and decrease the collateral effects caused by the reference drugs. In this systematic review we investigated publications that described a combination of nonconventional treatment for cutaneous and mucocutaneous with pentavalent antimonials. A literature review was performed in the databases Web of Knowledge and PubMed in the period from 01st of December 2004 to 01st of June 2017, according to Prisma statement. Only clinical trials involving the treatment for cutaneous or mucocutaneous leishmaniasis, in English, and with available abstract were added. Other types of publications, such as reviews, case reports, comments to the editor, letters, interviews, guidelines, and errata, were excluded. Sixteen articles were selected and the pentavalent antimonials were administered in combination with pentoxifylline, granulocyte macrophage colony-stimulating factor, imiquimod, intralesional sodium stibogluconate, ketoconazole, silver-containing polyester dressing, lyophilized LEISH-F1 protein, cryotherapy, topical honey, and omeprazole. In general, the combined therapy resulted in high rates of clinical cure and when relapse or recurrence was reported, it was higher in the groups treated with pentavalent antimonials alone. The majority of the articles included in this review showed that cure rate ranged from 70 to 100% in patients treated with the combinations. Serious adverse effects were not observed in patients treated with drugs combination. The combination of other drugs or treatment modalities with pentavalent antimonials has proved to be effective for cutaneous and mucocutaneous leishmaniasis and for most seemed to be safe. However, new randomized, controlled, and multicentric clinical trials with more robust samples should be performed, especially the combination with immunomodulators.

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Preclinical photodynamic therapy in Spain 1: Chemical and photophysical studies on porphycenes and other photosensitizers

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424609000541 ◽

2009 ◽

Vol 13 (04n05) ◽

pp. 528-536 ◽

Cited By ~ 2

Author(s):

David Sánchez-García ◽

José I. Borrell ◽

Xavier Batllori ◽

Jordi Teixidó ◽

Xavier Tomás ◽

...

Keyword(s):

Cell Death ◽

Photodynamic Therapy ◽

Adverse Effects ◽

Singlet Oxygen ◽

Research Group ◽

High Selectivity ◽

Spectroscopic Techniques ◽

Efficacy And Safety ◽

Photophysical Studies ◽

Cell Death Mechanisms

Photodynamic therapy (PDT) is a rapidly expanding alternative to the treatment of solid tumors and other highly-proliferative diseases due to its many attractive features: high selectivity, repeatability, and lack of serious adverse effects. The five drugs approved for use in PDT to date suffer from different problems that limit their efficacy and safety. Current understanding of cell death mechanisms offers an opportunity for the development of new, more efficient and safer drugs. This highlight describes the efforts of our research group in the PDT field: chemical development of porphycenes as PDT photosensitizers, photophysical screening of new families of potential PDT agents, and development of spectroscopic techniques for directly monitoring singlet oxygen and thus better understand the production, diffusion, and reactivity of this primary cytotoxic species in cells.

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

Frontiers in Oncology ◽

10.3389/fonc.2020.610472 ◽

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.

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Role of Phytochemicals in the Treatment of Breast Cancer: Natural Swords battling Cancer Cells

Current Cancer Therapy Reviews ◽

10.2174/1573394716666210106123255 ◽

2021 ◽

Vol 16 ◽

Author(s):

Rajni Sawanny ◽

Sheersha Pramanik ◽

Unnati Agarwal

Keyword(s):

Breast Cancer ◽

Molecular Mechanisms ◽

Low Cost ◽

Epigallocatechin Gallate ◽

Cancer Therapeutics ◽

Treatment Modalities ◽

Breast Cancer Patients ◽

Scientific Validity ◽

Phytochemical Study ◽

Treat Breast Cancer

: Breast cancer is the most common type of malignancy among ladies (around 30% of newly diagnosed patients every year). To date, various modern treatment modalities for breast cancer, such as radiotherapy, surgical method, hormonal therapy, and chemotherapeutic drug utilisation, are available. However, adverse drug reactions, therapeutic resistance, metastasis, or cancer reoccurrence chances remain the primary causes of mortality for breast cancer patients. To overcome all the potential drawbacks, we need to investigate novel techniques and strategies previously not considered and treat breast cancer effectively with safety and efficacy. For centuries, we utilise phytochemicals to treat various diseases because of their safety, low-cost & least or no side effects. Recently, naturally produced phytochemicals gain immense attention as potential breast cancer therapeutics because of their ideal characteristics; for instance, they operate via modulating molecular pathways associated with cancer growth and progression. The primary mechanism involves inhibition of cell proliferation, angiogenesis, migration, invasion, increasing anti-oxidant status, initiation of the arrest of the cell cycle, and apoptosis. Remedial viability gets effectively enhanced when phytochemicals work as adjuvants with chemotherapeutic drugs. This comprehensive review revolves around the latest chemopreventive, chemotherapeutic, and chemoprotective treatments with their molecular mechanisms to treat breast cancer by utilising phytochemicals such as vinca alkaloids, resveratrol, curcumin, paclitaxel, silibinin, quercetin, genistein and epigallocatechin gallate. The authors wish to extend the field of phytochemical study for its scientific validity and its druggability.

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Metabolic Profiling Analysis Reveals the Potential Contribution of Barley Sprouts against Oxidative Stress and Related Liver Cell Damage in Habitual Alcohol Drinkers

Antioxidants ◽

10.3390/antiox10030459 ◽

2021 ◽

Vol 10 (3) ◽

pp. 459

Author(s):

Hyerin Park ◽

Eunok Lee ◽

Yunsoo Kim ◽

Hye Yoon Jung ◽

Kwang-Min Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Liver ◽

Molecular Mechanisms ◽

Learning Algorithm ◽

Controlled Trial ◽

Liver Fat ◽

Glutathione Metabolism ◽

Ros Generation ◽

Potential Contribution ◽

Glutamyl Transferase

Chronic excessive alcohol consumption is associated with multiple liver defects, such as steatosis and cirrhosis, mainly attributable to excessive reactive oxygen species (ROS) production. Barley sprouts (Hordeum vulgare L.) contain high levels of polyphenols that may serve as potential antioxidants. This study aimed to investigate whether barley sprouts extract powder (BSE) relieves alcohol-induced oxidative stress and related hepatic damages in habitual alcohol drinkers with fatty liver. In a 12-week randomized controlled trial with two arms (placebo or 480 mg/day BSE; n = 76), we measured clinical markers and metabolites at the baseline and endpoint to understand the complex molecular mechanisms. BSE supplementation reduced the magnitude of ROS generation and lipid peroxidation and improved the glutathione antioxidant system. Subsequent metabolomic analysis identified alterations in glutathione metabolism, amino acid metabolism, and fatty acid synthesis pathways, confirming the role of BSE in glutathione-related lipid metabolism. Finally, the unsupervised machine learning algorithm indicated that subjects with lower glutathione reductase at the baseline were responders for liver fat content, and those with higher fatigue and lipid oxidation were responders for γ-glutamyl transferase. These findings suggest that BSE administration may protect against hepatic injury by reducing oxidative stress and changing the metabolism in habitual alcohol drinkers with fatty liver.

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Corrigendum to “Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells” [Biomed. Pharmacother. 123 (2020) 109794]

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.111175 ◽

2020 ◽

pp. 111175

Author(s):

Tairine Zara Lopes ◽

Fabio Rogério de Moraes ◽

Antonio Claudio Tedesco ◽

Raghuvir Krishnaswamy Arni ◽

Paula Rahal ◽

...

Keyword(s):

Photodynamic Therapy ◽

Renal Carcinoma ◽

Carcinoma Cells ◽

Ros Generation ◽

Renal Carcinoma Cells

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Nonylphenol Induces Apoptosis through ROS/JNK Signaling in a Spermatogonia Cell Line

International Journal of Molecular Sciences ◽

10.3390/ijms22010307 ◽

2020 ◽

Vol 22 (1) ◽

pp. 307

Author(s):

Hyun-Jung Park ◽

Ran Lee ◽

Hyunjin Yoo ◽

Kwonho Hong ◽

Hyuk Song

Keyword(s):

Molecular Mechanisms ◽

Mapk Signaling ◽

Ros Generation ◽

Dependent Manner ◽

Jnk Signaling ◽

Apoptosis Markers ◽

Testicular Size ◽

Spermatogonia Cell ◽

Induced Apoptosis ◽

Dose Dependent

Nonylphenol (NP) is an endocrine-disruptor chemical that negatively affects reproductive health. Testes exposure to NP results in testicular structure disruption and a reduction in testicular size and testosterone levels. However, the effects of NP on spermatogonia in testes have not been fully elucidated. In this study, the molecular mechanisms of NP in GC-1 spermatogonia (spg) cells were investigated. We found that cell viability significantly decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to NP. Furthermore, the expression levels of the pro-apoptotic proteins increased, whereas anti-apoptosis markers decreased in NP-exposed GC-1 spg cells. We also found that NP increased reactive oxygen species (ROS) generation, suggesting that ROS-induced activation of the MAPK signaling pathway is the molecular mechanism of NP-induced apoptosis in GC-1 spg cells. Thus, NP could induce c-Jun phosphorylation; dose-dependent expression of JNK, MKK4, p53, and p38; and the subsequent inhibition of ERK1/2 and MEK1/2 phosphorylation. The genes involved in apoptosis and JNK signaling were also upregulated in GC-1 spg cells treated with NP compared to those in the controls. Our findings suggest that NP induces apoptosis through ROS/JNK signaling in GC-1 spg cells.

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The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

Cancers ◽

10.3390/cancers13133169 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3169

Author(s):

Kevin Doello ◽

Cristina Mesas ◽

Francisco Quiñonero ◽

Gloria Perazzoli ◽

Laura Cabeza ◽

...

Keyword(s):

Pancreatic Cancer ◽

Sodium Selenite ◽

Molecular Mechanisms ◽

Combined Therapy ◽

Significant Inhibition ◽

In Vivo Studies ◽

C57bl Mice ◽

Migration Capacity

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.

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