Ethosomes and lipid-coated chitosan nanocarriers for skin delivery of a chlorophyll derivative: A potential treatment of squamous cell carcinoma by photodynamic therapy

Nasr, Soad M.; Rady, Mai; Gomaa, Iman; Syrovets, Tatiana; Simmet, Thomas; Fayad, Walid; Abdel‐Kader, Mahmoud H.

doi:10.1016/j.ijpharm.2019.118528

Cited by 50 publications

(33 citation statements)

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“…The light doses used in this study were 12 J/cm 2 and 60 J/cm 2 . Higher doses have previously been shown to be cytotoxic [ 17 ]. Squamous cell carcinoma cells (1 × 10 3 cells/well) were seeded in a 96-well plate and incubated overnight under standard culture conditions (37 °C, 5% CO 2 ).…”

Section: Methodsmentioning

confidence: 99%

“…Ce6 ethosomes were diluted to the desired concentration in DMEM complete medium and incubated with the cells for additional 24 h. Thereafter, cells were irradiated with a monochromatic red laser (652 ± 5 nm) with light doses equivalent to 12 and 60 J/cm 2 . The photodynamic effect of Ce6 ethosomes was assessed using the colorimetric MTT assay 24 h later [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…A431 squamous cell carcinoma cells or normal human skin BJ fibroblasts were seeded at a density of 5 × 10 4 cells/well in 200 µL medium DMEM/F-12, 1% streptomycin, and 10% FBS. After 5 days of spheroid formation, the supernatant was cautiously substituted with fresh culture medium prior to treatment [ 17 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…The combination of alcohol and soft phospholipid vesicles in ethosomes yields ultradeformable properties and allows for greater penetration into deeper skin layers [ 15 , 16 ]. In our previous study, the photosensitizer ferrous chlorophyllin loaded into ethosomes exhibited higher skin penetration compared to ferrous chlorophyllin loaded into lipid-coated chitosan particles, despite the fact that the latter particles were half the size of ethosomes [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models

et al. 2020

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Photodynamic therapy (PDT) is a non-invasive treatment strategy that includes the combination of three components—a photosensitizer, a light source, and tissue oxygen. PDT can be used for the treatment of skin diseases such as squamous cell carcinoma. The photosensitizer used in this study is the naturally derived chlorophyll derivative chlorin e6 (Ce6), which was encapsulated in ultradeformable ethosomes. Singlet oxygen production by Ce6 upon laser light irradiation was not significantly affected by encapsulation into ethosomes. PDT of squamous cell carcinoma cells treated with Ce6 ethosomes triggered increased mitochondrial superoxide levels and increased caspase 3/7 activity, resulting in concentration- and light-dose-dependent cytotoxicity. Ce6 ethosomes showed good penetration into 3D squamous cell carcinoma spheroids, which upon laser light irradiation exhibited reduced size, proliferation, and viability. The PDT effect of Ce6 ethosomes was specific and showed higher cytotoxicity against squamous cell carcinoma spheroids compared to normal skin fibroblast spheroids. In addition, PDT treatment of squamous cell carcinoma xenografts grown on chorioallantoic membranes of chick eggs (CAM) exhibited reduced expression of Ki-67 proliferation marker and increased terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining, indicating reduced proliferation and activation of apoptosis, respectively. The results demonstrate that Ce6-loaded ethosomes represent a convenient formulation for photodynamic treatment of squamous cell carcinoma.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models

et al. 2020

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“…Despite that, the array of photoproperties, biocompatibility and natural abundance of chlorophyll make it a suitable sonosensitizer candidate for SDT application [19], even if the hydrophobicity of the chlorophyll macrocycle is a limit that cuts down the applications in aqueous environment. Therefore, some chlorophyll derivatives have been obtained and associated to colloidal carriers, such as micelles, ethosomes, liposomes, and nanoparticles, but only for PDT applications [20][21][22][23][24][25]. This is the first work that investigates chlorophyll as it is in nature, such as a mixture of different chlorophyll molecules, including chlorophyll a, b and pheophytin a.…”

Section: Introductionmentioning

confidence: 99%

Exploiting Lipid and Polymer Nanocarriers to Improve the Anticancer Sonodynamic Activity of Chlorophyll

et al. 2020

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Sonodynamic therapy is an emerging approach that uses low-intensity ultrasound to activate a sonosensitizer agent triggering its cytotoxicity for selective cancer cell killing. Several molecules have been proposed as sonosensitizer agents, but most of these, as chlorophyll, are strongly hydrophobic with a low selectivity towards cancer tissues. Nanocarriers can help to deliver more efficiently the sonosensitizer agents in the target tumor site, increasing at the same time their sonodynamic effect, since nanosystems act as cavitation nuclei. Herein, we propose the incorporation of unmodified plant-extracted chlorophyll into nanocarriers with different composition and structure (i.e., liposomes, solid lipid nanoparticles and poly(lactic-co-glycolic acid) nanoparticles) to obtain aqueous formulations of this natural pigment. The nanocarriers have been deeply characterized and then incubated with human prostatic cancer cells (PC-3) and spheroids (DU-145) to assess the influence of the different formulations on the chlorophyll sonodynamic effect. The highest sonodynamic cytotoxicity was obtained with chlorophyll loaded into poly(lactic-co-glycolic acid) nanoparticles, showing promising results for future clinical investigations on sonodynamic therapy.

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Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Sebak,

Abdel‐Halim,

Abdelrahman

et al. 2024

Advanced Therapeutics

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The complexity of the tumor microenvironment (TME) and nutrient competition represent the main causes of therapy resistance in cancers, including malignant melanoma (MM). Photodynamic therapy (PDT), through a cascade of events including its ability to induce significant immune responses, causes tumor eradication. However, the high pigmentation level of melanoma, lack of adequate accumulation of photosensitizers (PSs) in the target tissue as well as their nonspecific toxicity represent three main obstacles to obtaining satisfactory responses in melanoma. To prevail over these challenges, this study employed a depigmentation strategy followed by a nano‐mediated topical application of PDT using a chlorophyllin derivative as PS, focusing on evaluation of the immunomodulatory and metabolic regulatory axes of PDT in melanoma. Photo‐immunomodulation was assessed in a melanoma mouse model using a nanocarrier system of the PS. Markers of the immunosuppressive microenvironment and T cell exhaustion, as independent immune hallmarks, were quantified. The histopathology of spleen and skin/tumor was evaluated. The amino acid profile was quantified from normal skin or tumor biopsies using UHPLC‐MS/MS. Around 80% of the 300 nm transethosomal ferrous chlorophyllin (fC‐TEs) were retained in the tumor over 24 h upon topical application. Arbutin 2% gel not only decreased the melanin content of tumors, but also regulated the expression of interleukin 12 (IL‐12), IL‐10, transforming growth factor beta (TGF‐β) and tumor necrosis factor alpha (TNF‐α). Additionally, the nano‐mediated PDT strategy decreased the expression of programmed cell death protein 1 (PD‐1) & its ligand 1 (PD‐L1) and reduced the activity of arginase 1 (Arg1) through an upregulation of miRNA155. A mild recruitment of megakaryocytes (MKs) was observed in the spleen of the PDT group. This special localization of MKs depicts effector immune properties. Lastly, the combination of PDT and arbutin restored the normal tissue levels of arginine (Arg), glutamine (Gln) and lavished those of tryptophan (Trp). Nano‐mediated PDT represents a novel immunotherapeutic approach in melanoma by a triple modulation of the immune suppressive TME, immune checkpoint signaling, and reprogrammed tumor metabolism.This article is protected by copyright. All rights reserved

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Ethosomes and lipid-coated chitosan nanocarriers for skin delivery of a chlorophyll derivative: A potential treatment of squamous cell carcinoma by photodynamic therapy

Cited by 50 publications

References 43 publications

A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models

A Naturally Derived Carrier for Photodynamic Treatment of Squamous Cell Carcinoma: In Vitro and In Vivo Models

Exploiting Lipid and Polymer Nanocarriers to Improve the Anticancer Sonodynamic Activity of Chlorophyll

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

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