Current state of the nanoscale delivery systems for temoporfin-based photodynamic therapy: Advanced delivery strategies

Yakavets, Ilya; Millard, Marie; Zorin, Vladimir; Lassalle, Henri-Pierre; Bezdetnaya, Lina

doi:10.1016/j.jconrel.2019.05.035

Cited by 71 publications

(49 citation statements)

References 145 publications

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“…The efficiency of PDT with different photosensitizers, including meta-tetra-(hydroxyphenyl)chlorin (mTHPC), is still restricted by a moderate tumor selectivity of PSs, that is, elevated skin sensitivity after irradiation, thus reducing its clinical application. In order to overcome these limitations, a nanovectorization strategy with phospholipidic structures was developed and proposed for enhanced PDT [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models

et al. 2020

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Extracellular vesicles (EVs), derived from the cell, display a phospholipid bilayer membrane that protects the cargo molecules from degradation and contributes to increasing their stability in the bloodstream and tumor targeting. EVs are interesting in regard to the delivery of photosensitizers (PSs) used in the photodynamic therapy (PDT), as they allow us to overcome the limitations observed with liposomes. In fact, liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (mTHPC) (Foslip®), one of the most potent clinically approved PSs, is rapidly destroyed in circulation, thus decreasing in vivo PDT efficacy. mTHPC-EV uptake was evaluated in vitro in a 3D human colon HT-29 microtumor and in vivo study was performed in HT-29 xenografted mice. The obtained data were compared with Foslip®. After intravenous injection of the mTHPC formulations, biodistribution, pharmacokinetics and PDT-induced tumor regrowth were evaluated. In a 3D model of cells, mTHPC-EV uptake featured a deeper penetration after 24h incubation compared to liposomal mTHPC. In vivo results showed a considerable improvement of 33% tumor cure with PDT treatment applied 24h after injection, while 0% was observed after Foslip®/PDT. Moreover, 47 days were required to obtain ten times the initial tumor volume after mTHPC-EVs/PDT compared to 30 days for liposomal mTHPC. In conclusion, compared to Foslip®, mTHPC-EVs improved mTHPC biodistribution and PDT efficacy in vivo. We deduced that a major determinant factor for the improved in vivo PDT efficacy is the deep mTHPC intratumor penetration.

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Section: Introductionmentioning

confidence: 99%

mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models

et al. 2020

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“…The absorbance of the micellar dispersion diluted in DMSO was recorded at 651.5 nm using a UV-2450 Shimadzu spectrophotometer (Kyoto, Japan) and calibration was done using a series of standard solutions of mTHPC in DMSO to determine the mTHPC loading [24]. The loading efficiency (LE) and loading capacity (LC) of mTHPC were calculated using the following Equations (1) and (2), respectively:…”

Section: Preparation and Characterization Of Empty And Mthpc-loaded Mmentioning

confidence: 99%

“…Photodynamic therapy (PDT) is a minimally invasive form of therapy that has been approved for treatment of various types of cancers, including head and neck tumors, basal cell carcinoma, cervical, endobronchial, esophageal, bladder, and gastric cancers [1,2]. Compared to conventional treatments, such as surgery, radiation and chemotherapy, PDT has important advantages, including reduced toxicity for healthy tissues, lack of drug resistance mechanisms, and favorable cosmetic outcomes.…”

Section: Introductionmentioning

confidence: 99%

π-π-Stacked Poly(ε-caprolactone)-b-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy

et al. 2020

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To improve the in vivo stability of poly(ε-caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles and cargo retention by π-π stacking interactions, pendant aromatic rings were introduced by copolymerization of ε-caprolactone with benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (TMC-Bz). It was shown that the incorporation of aromatic rings yielded smaller micelles (18-30 nm) with better colloidal stability in PBS than micelles without aromatic groups. The circulation time of i.v. injected micelles containing multiple pendant aromatic groups was longer (t 1 /2-α:~0.7 h; t 1 /2-β: 2.9 h) than that of micelles with a single terminal aromatic group (t 1 /2 < 0.3 h). In addition, the in vitro partitioning of the encapsulated photosensitizer (meta-tetra(hydroxyphenyl)chlorin, mTHPC) between micelles and human plasma was favored towards micelles for those that contained the pendant aromatic groups. However, this was not sufficient to fully retain mTHPC in the micelles in vivo, as indicated by similar biodistribution patterns of micellar mTHPC compared to free mTHPC, and unequal biodistribution patterns of mTHPC and the host micelles. Our study points out that more detailed in vitro methods are necessary to more reliably predict in vivo outcomes. Furthermore, additional measures beyond π-π stacking are needed to stably incorporate mTHPC in micelles in order to benefit from the use of micelles as targeted delivery systems.Pharmaceutics 2020, 12, 338 2 of 26 and can subsequently transfer its energy to molecular oxygen to yield singlet oxygen species (ROS), which are highly reactive with biomolecules present in cytoplasma or cell membranes, leading to cell death [5,6]. Effective cancer PDT is, however, hindered by some undesired properties in PS. Most PS molecules-including the clinically approved second generation PS, meta-tetra(hydroxyphenyl)chlorin (mTHPC)-are highly hydrophobic due to the extended delocalized aromatic π electron system. This promotes non-specific binding to cells, resulting in unspecific distribution of PS in healthy tissues (i.e., no selective accumulation of the PS in tumorous tissues), which can cause skin toxicity [7][8][9]. Moreover, the poor water solubility caused by the high hydrophobicity makes PS prone to aggregation in aqueous solutions, leading to lower ROS generation and decreased therapeutic efficacy [9][10][11].Loading of PS in polymeric micelles is a promising approach to address these challenges [12]. Polymeric micelles are self-assembled nanostructures based on amphiphilic block copolymers formed in an aqueous solution and have been extensively investigated as drug delivery systems, particularly for the targeted delivery of hydrophobic drugs [13][14][15][16]. Polymeric micelles are characterized by a well-defined structure, containing a hydrophobic core and a hydrophilic shell. The micellar core has a high capacity to accommodate hydrophobic compounds, including photosensitizers, while the hydrophilic shell, which is mostly composed of poly(ethylene glycol) (PEG), can result in...

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“…Photodynamic therapy (PDT) is considered an alternative to radiation therapy and chemotherapy, which are the most common forms of cancer treatment. Researchers have been exploring new strategies based on nanotechnology to increase PDT efficiency in recent years [ 1 ]. PDT is a procedure that has been proven to be extremely useful for the treatment of many forms of cancer and is considered to be a minimally invasive approach [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Progress in Clinical Trials of Photodynamic Therapy for Solid Tumors and the Role of Nanomedicine

Alsaab

Alghamdi

Alotaibi

et al. 2020

Cancers

105

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Current research to find effective anticancer treatments is being performed on photodynamic therapy (PDT) with increasing attention. PDT is a very promising therapeutic way to combine a photosensitive drug with visible light to manage different intense malignancies. PDT has several benefits, including better safety and lower toxicity in the treatment of malignant tumors over traditional cancer therapy. This reasonably simple approach utilizes three integral elements: a photosensitizer (PS), a source of light, and oxygen. Upon light irradiation of a particular wavelength, the PS generates reactive oxygen species (ROS), beginning a cascade of cellular death transformations. The positive therapeutic impact of PDT may be limited because several factors of this therapy include low solubilities of PSs, restricting their effective administration, blood circulation, and poor tumor specificity. Therefore, utilizing nanocarrier systems that modulate PS pharmacokinetics (PK) and pharmacodynamics (PD) is a promising approach to bypassing these challenges. In the present paper, we review the latest clinical studies and preclinical in vivo studies on the use of PDT and progress made in the use of nanotherapeutics as delivery tools for PSs to improve their cancer cellular uptake and their toxic properties and, therefore, the therapeutic impact of PDT. We also discuss the effects that photoimmunotherapy (PIT) might have on solid tumor therapeutic strategies.

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Current state of the nanoscale delivery systems for temoporfin-based photodynamic therapy: Advanced delivery strategies

Cited by 71 publications

References 145 publications

mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models

mTHPC-Loaded Extracellular Vesicles Significantly Improve mTHPC Diffusion and Photodynamic Activity in Preclinical Models

π-π-Stacked Poly(ε-caprolactone)-b-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy

Progress in Clinical Trials of Photodynamic Therapy for Solid Tumors and the Role of Nanomedicine

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