Cyclodextrin nanosponge as a temoporfin nanocarrier: Balancing between accumulation and penetration in 3D tumor spheroids

Yakavets, Ilya; Guereschi, Chloe; Lamy, Laureline; Кравченко, И. Е.; Lassalle, Henri-Pierre; Zorin, Vladimir; Bezdetnaya, Lina

doi:10.1016/j.ejpb.2020.06.022

Cited by 17 publications

(11 citation statements)

References 42 publications

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“…The analysis of images was performed using ImageJ (NIH, USA) software. Custom macros for ImageJ was used to calculate the profile of dye penetration into the spheroids 43,44 . Briefly, the spheroid area was divided into 50 concentric rims with a linearly decreasing diameter.…”

Section: Characterization Of Spheroids Fluorescence Microscopy and Immmentioning

confidence: 99%

Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study

Yakavets

François

Benoit

et al. 2020

Sci Rep

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Radiation-induced fibrosis (RIF) is the main late radiation toxicity in breast cancer patients. Most of the current 3D in vitro breast cancer models are composed by cancer cells only and are unable to reproduce the complex cellular homeostasis within the tumor microenvironment to study RIF mechanisms. In order to account complex cellular interactions within the tumor microenvironment, an advanced 3D spheroid model, consisting of the luminal breast cancer MCF-7 cells and MRC-5 fibroblasts, was developed. The spheroids were generated using the liquid overlay technique in culture media into 96-well plates previously coated with 1% agarose (m/v, in water). In total, 21 experimental setups were tested during the optimization of the model. The generated spheroids were characterized using fluorescence imaging, immunohistology and immunohistochemistry. The expression of ECM components was confirmed in co-culture spheroids. Using α-SMA staining, we confirmed the differentiation of healthy fibroblasts into myofibroblasts upon the co-culturing with cancer cells. The induction of fibrosis was studied in spheroids treated 24 h with 10 ng/mL TGF-β and/or 2 Gy irradiation. Overall, the developed advanced 3D stroma-rich in vitro model of breast cancer provides a possibility to study fibrosis mechanisms taking into account 3D arrangement of the complex tumor microenvironment.

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Section: Characterization Of Spheroids Fluorescence Microscopy and Immmentioning

confidence: 99%

Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study

Yakavets

François

Benoit

et al. 2020

Sci Rep

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“…As such, β-CD has been used to form nano-porous polymers [ 15 ]. The rising popularity of NSs as the material of choice over native CD is mainly due to their higher entrapment capacities, control over particle size and their ability to be regenerated and reutilized [ 16 , 17 , 18 , 19 ]. NSs can also improve the physicochemical properties of the guest molecules, such as solubility and stability, and absorb liquids into their nano-porous structure to convert liquid materials into a solid form [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…NSs have been proven to be safe, non-toxic, biodegradable, and of low cost [ 22 , 23 , 24 ]. As such, NSs have gained attention in targeted drug delivery research aimed at improving the efficacy of chemotherapies and reducing the adverse effects related to the drugs [ 16 , 17 , 18 , 20 , 25 , 26 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan

Salazar

Yutronic

Kogan

et al. 2021

IJMS

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This article describes the synthesis and characterization of β-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV–Vis, and proton nuclear magnetic resonance (1H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV–Vis. Drug release studies using NSs synthesized with different molar ratios of β-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible.

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“…Furthermore, one could expect that Me-β-CD could modulate the cellular uptake in blood cancer cells. Given the increasing interest in β-CDs as a component of hybrid nanocarriers (e.g., drug-in-cyclodextrin-in-liposome [ 38 , 39 , 40 ], cyclodextrin-based polymers [ 41 ]), the detailed analysis of mTHPC distribution provides a better understanding of how we can alter biodistribution and pharmacokinetics of mTHPC using nanotechnology aiming for a high therapeutic efficiency of mTHPC-PDT with low side effects.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

et al. 2021

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Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

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Cyclodextrin nanosponge as a temoporfin nanocarrier: Balancing between accumulation and penetration in 3D tumor spheroids

Cited by 17 publications

References 42 publications

Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study

Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan

Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

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