Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids

Gaio, Elisa; Scheglmann, Dietrich; Reddi, Elena; Moret, Francesca

doi:10.1016/j.jphotobiol.2016.05.011

Cited by 62 publications

(41 citation statements)

References 29 publications

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“…Despite the external localization of the PS, photodamage were observed in the internal region of spheroids, suggesting the diffusion of the singlet oxygen, a highly cytotoxic form of reactive oxygen species produced by the photodynamic reaction. 59 Of big interest is the consistency of the results obtained in spheroids with tumors established from the same cell type. On the basis of in vivo imaging in tumor-bearing mice, a strong parallel exists in the capacity of NPs to accumulate and to penetrate in cell spheroids as compared with tumor tissue.…”

mentioning

confidence: 99%

“…In this regard, 3D in vitro models and above all MCTS have been applied for evaluating the NP potential to accumulate and penetrate in depth the tumor tissue. 20,34,[56][57][58][59] Determination of free or drug-loaded NPs' distribution and concentration in spheroids can be performed by various techniques. The distribution of gold NPs in MCTS could be precisely assessed with transmission electronic microscopy (TEM), 60,61 while fluorescence microscopy was successfully applied for the detection of dye-labeled NPs.…”

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confidence: 99%

“…In this case, the NPs are either labeled with fluorescent probes, 34,57,62-64 specific dyes or loaded with fluorescent drugs such as doxorubicin (DOX), 58,[65][66][67][68] Oregon Green 488 Taxol, 20 or porphyrin-based photosensitizers (PSs). 59,69 Estimation of drug concentration in MCTS could be done by high-performance liquid chromatography (HPLC), 20 flow cytometry or chemical extraction with successive fluorescence measurements. 43,44,57,64 After incubation, MCTS is collected and embedded in special medium as tissue-Tek before being cut in thin sections (~5 µm).…”

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confidence: 99%

“…20,34,58,59,62,64,70 NP penetration can also be evaluated in intact fixed MCTS [64][65][66] or in intact living MCTS by using confocal laser scanning microscopy. 34,71 An important lesson to draw from these experiments has been the excellence of the MCTS model to determine the main factors hindering or favoring NP penetration.…”

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confidence: 99%

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Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

108

107

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The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS) model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM) components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a better comprehension of the interactions between NPs and tumor components that affect tumor drug delivery. MCTS is particularly suitable for the high-throughput screening of new nanodrugs.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

108

107

View full text Add to dashboard Cite

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“…Visudyne ® , the non-PEGylated liposomal formulation of Verteporfin ® is however the first and unique example of PS nano-formulation approved by FDA since 2000 for the treatment of age-related macular degeneration [127]. Very promising and extensively studied in vitro [128][129][130] and in vivo [131,132] [133]. Multicellular spheroids are in vitro avascular tumor models, mimicking the in vivo tumor architecture much better than cell monolayers and are very useful for investigating PS penetration ability and light/PS-triggered ROS production in the inner region of tumor mass.…”

Section: Lipid-based Nanocarriersmentioning

confidence: 99%

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

Moret

Reddi

2017

J. Porphyrins Phthalocyanines

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This review briefly summaries the principles and mechanisms of action of photodynamic therapy (PDT) as concerns its application in the oncological field, highlighting its drawbacks and some of the strategies that have been or are being explored to overcome them. The major aim is to increase the efficiency and selectivity of the photosensitizer (PS) uptake in the cancer cells for optimizing the PDT effects on tumors while sparing normal cells. Some attempts to achieve this are based on the conjugation of the PS to biomolecules (small ligands, peptides) functioning as carriers with the ability to efficiently penetrate cells and/or specifically recognize and bind proteins/receptors overexpressed on the surface of cancer cells. Alternatively, the PS can be entrapped in nanocarriers derived from various types of materials that can target the tumor by exploiting the enhanced permeability and retention (EPR) effects. The use of nanocarriers is particularly attractive because it allows the simultaneous delivery of more than one drug with the possibility of combining PDT with other therapeutic modalities.

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One‐Photon and Two‐Photon Photophysical Properties of Tetrafunctionalized 5,10,15,20‐tetrakis(m‐hydroxyphenyl)chlorin (Temoporfin) Derivatives as Potential Two‐Photon‐Induced Photodynamic Therapy Agents

et al. 2022

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Photodynamic therapy (PDT) is a cancer treatment, which exploits a photosensitizing drug and light to produce reactive oxygen species that can cause selective damage to the target tissue. The second‐generation photosensitizer 5,10,15,20‐tetrakis(m‐hydroxyphenyl)chlorin (m‐THPC) is a widely used, clinically tested, and commercially available drug with the market formulation known as Foscan. m‐THPC was used as a starting point to obtain a library of compounds with improved optical properties. Substitution, esterification and Sonogashira coupling reactions were employed to modify the m‐THPC skeleton. Aldehyde and carboxylic acid moieties provided the possibility to enhance the two‐photon absorption (TPA) cross‐section while being suitable synthetic handles in the design of drug delivery systems. Characterization of their linear photophysical properties (fluorescence quantum yield, fluorescence lifetime and singlet oxygen quantum yield) was followed by the evaluation of their potential use in a non‐linear absorption regime. The calculated TPA cross‐section values indicate even a 2.6‐fold enhancement at the TPA maximum (69.3±10.0 GM), compared to m‐THPC (26.7±4.0 GM), which proves that functionalization of the m‐THPC core leads to the improvement of the non‐linear optical properties. Thus, tetrafunctionalized m‐THPC derivatives are promising candidates for application in two‐photon induced PDT.

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Uptake and photo-toxicity of Foscan®, Foslip® and Fospeg® in multicellular tumor spheroids

Cited by 62 publications

References 29 publications

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

One‐Photon and Two‐Photon Photophysical Properties of Tetrafunctionalized 5,10,15,20‐tetrakis(m‐hydroxyphenyl)chlorin (Temoporfin) Derivatives as Potential Two‐Photon‐Induced Photodynamic Therapy Agents

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