Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids

Yakavets, Ilya; Millard, Marie; Lamy, Laureline; François, Aurélie; Scheglmann, Dietrich; Wiehe, Arno; Lassalle, Henri-Pierre; Zorin, Vladimir; Bezdetnaya, Lina

doi:10.3390/cancers11091366

Cited by 16 publications

(25 citation statements)

References 28 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analysis of images was performed with ImageJ (NIH, Bethesda, MD, USA) software. To estimate the dye penetration profile in spheroid, the special macros was proposed [33]. Briefly, the spheroid area was divided into 100 concentric rims with a linearly decreasing diameter.…”

Section: Methodsmentioning

confidence: 99%

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

Yakavets

Samuel

François

et al. 2019

JCM

View full text Add to dashboard Cite

Conventional 3D multicellular tumor spheroids of head and neck squamous cell carcinoma (HNSCC) consisting exclusively of cancer cells have some limitations. They are compact cell aggregates that do not interact with their extracellular milieu, thus suffering from both insufficient extracellular matrix (ECM) deposition and absence of different types of stromal cells. In order to better mimic in vivo HNSCC tumor microenvironment, we have constructed a 3D stroma-rich in vitro model of HNSCC, using cancer-associated MeWo skin fibroblasts and FaDu pharynx squamous cell carcinoma. The expression of stromal components in heterospheroids was confirmed by immunochemical staining. The generated co-culture FaDu/MeWo spheroids were applied to study penetration, distribution and antitumor efficacy of photoactive drugs such as Temoporfin and Chlorin e6 used in the photodynamic therapy flow cytometry and fluorescence microscopy techniques. We also investigated the distribution of photodiagnostic agent Indocyanine Green. We demonstrated that the presence of stroma influences the behavior of photoactive drugs in different ways: (i) No effect on Indocyanine Green distribution; (ii) lower accumulation of Chlorin e6; (iii) better penetration and PDT efficiency of Temoporfin. Overall, the developed stroma-rich spheroids enlarge the arsenal of in vitro pre-clinical models for high-throughput screening of anti-cancer drugs.

show abstract

Section: Methodsmentioning

confidence: 99%

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

Yakavets

Samuel

François

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…A novel perspective biogenic delivery nanoplatforms based on naturally-derived extracellular vesicles (mTHPC-EVs) have been recently investigated, showing improved plasma stability and increased PDT efficiency compared with Foslip ® [ 14 ]. Meanwhile, drug-in-cyclodextrin-in-liposomes (mTHPC-DCL) have been recently proposed to ensure the deep penetration of mTHPC into the tumor tissue [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids

et al. 2021

View full text Add to dashboard Cite

Background Despite the highly expected clinical application of nanoparticles (NPs), the translation of NPs from lab to the clinic has been relatively slow. Co-culture 3D spheroids account for the 3D arrangement of tumor cells and stromal components, e.g., cancer-associated fibroblasts (CAFs) and extracellular matrix, recapitulating microenvironment of head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated how the stroma-rich tumor microenvironment affects the uptake, penetration, and photodynamic efficiency of three lipid-based nanoformulations of approved in EU photosensitizer temoporfin (mTHPC): Foslip® (mTHPC in conventional liposomes), drug-in-cyclodextrin-in-liposomes (mTHPC-DCL) and extracellular vesicles (mTHPC-EVs). Results Collagen expression in co-culture stroma-rich 3D HNSCC spheroids correlates with the amount of CAFs (MeWo cells) in individual spheroid. The assessment of mTHPC loading demonstrated that Foslip®, mTHPC-DCL and mTHPC-EVs encapsulated 0.05 × 10− 15 g, 0.07 × 10− 15 g, and 1.3 × 10− 15 g of mTHPC per nanovesicle, respectively. The mid-penetration depth of mTHPC NPs in spheroids was 47.8 µm (Foslip®), 87.8 µm (mTHPC-DCL), and 49.7 µm (mTHPC-EVs), irrespective of the percentage of stromal components. The cellular uptake of Foslip® and mTHPC-DCL was significantly higher in stroma-rich co-culture spheroids and was increasing upon the addition of serum in the culture medium. Importantly, we observed no significant difference between PDT effect in monoculture and co-culture spheroids treated with lipid-based NPs. Overall, in all types of spheroids mTHPC-EVs demonstrated outstanding total cellular uptake and PDT efficiency comparable to other NPs. Conclusions The stromal microenvironment strongly affects the uptake of NPs, while the penetration and PDT efficacy are less sensitive to the presence of stromal components. mTHPC-EVs outperform other lipid nanovesicles due to the extremely high loading capacity. The results of the present study enlarge our understanding of how stroma components affect the delivery of NPs into the tumors.

show abstract

“…57 To overcome the mTHPC aggregation issue, specific drug delivery strategies are currently being pursued, 58 in particular, the use of molecular hosts based on beta-cyclodextrin (b-CD) has been proposed. 59,60 The incorporation of mTHPC into betacyclodextrin 61 (Fig. 1d) and its release in model lipid membranes 62,63 ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Optical properties of photodynamic therapy drugs in different environments: the paradigmatic case of temoporfin

Aslanoglu

Yakavets

Zorin

et al. 2020

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

Matryoshka-Type Liposomes Offer the Improved Delivery of Temoporfin to Tumor Spheroids

Cited by 16 publications

References 28 publications

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids

Optical properties of photodynamic therapy drugs in different environments: the paradigmatic case of temoporfin

Contact Info

Product

Resources

About