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

Abstract

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.

Physical & Chemical Microwave Ablation (MWA) Enabled by Nonionic MWA Nanosensitizers Repress Incomplete MWA-Arised Liver Tumor Recurrence

“…The procedures are shown in Figure a. The as-prepared EF-DOX-Lip displays a well-defined spherical morphology with a particle size of 80 nm (Figure a,b), akin to that of previous reports. − An evident characteristic peak of DOX at 480 nm is observed (Figure c), suggesting the successful encapsulation of DOX in EF-DOX-Lip (9.82%). It is determined that the loading amount of DOX in EF-DOX-Lip varies as the drug/lipid ratio (by w/w) fluctuates, and it reaches the peak when the drug/lipid ratio (by w/w) is set as 1:10 (Figure S1a), where the encapsulation rate, particle size, and zeta potential almost fail to vary (Figure S1b–d).…”

Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

“…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.…”

Recent advances in lanthanide-doped up-conversion probes for theranostics

“…PDT has been clinically applied as a supplement to traditional therapy. Porphyrin is the first photosensitizer approved for this purpose ( Tian et al, 2020 ), and mTHPC (meso-tetra hydroxy phenyl chlorin), a second generation photosensitizer, has shown many excellent characteristics in photodynamic therapy ( Pinto et al, 2021 ; Yakavets et al, 2021 ; Yuan et al, 2021 ). In addition, chlorin dihydrogen E6 (Chlorin e6, Ce6), ZnPc and other photosensitizers have been widely used in scientific research although they have not been clinically approved ( Chen et al, 2021a ; Zhang et al, 2021a ; Chen et al, 2021b ; Hu et al, 2021 ; Lee et al, 2021 ; Shen et al, 2021 ; Zheng et al, 2021 ).…”