Nonequilibrium fluctuations of lipid membranes by the rotating motor protein F1F0-ATP synthase.

ATP synthase is a rotating membrane protein that synthesizes ATP through proton-pumping activity across the membrane. To unveil the mechanical impact of this molecular active pump on the bending properties of its lipid environment, we have functionally reconstituted the ATP synthase in giant unilamellar vesicles and tracked the membrane fluctuations by means of flickering spectroscopy. We find that ATP synthase rotates at a frequency of about 20 Hz, promoting large nonequilibrium deformations at discrete hot spots in lipid vesicles and thus inducing an overall membrane softening. The enhanced nonequilibrium fluctuations are compatible with an accumulation of active proteins at highly curved membrane sites through a curvature-protein coupling mechanism that supports the emergence of collective effects of rotating ATP synthases in lipid membranes.

Lipid Unsaturation Properties Govern the Sensitivity of Membranes to Photoinduced Oxidative Stress.

Unsaturated lipid oxidation is a fundamental process involved in different aspects of cellular bioenergetics; dysregulation of lipid oxidation is often associated with cell aging and death. To study how lipid oxidation affects membrane biophysics, we used a chlorin photosensitizer to oxidize vesicles of various lipid compositions and degrees of unsaturation in a controlled manner. We observed different shape transitions that can be interpreted as an increase in the area of the targeted membrane followed by a decrease. These area modifications induced by the chemical modification of the membrane upon oxidation were followed in situ by Raman tweezers microspectroscopy. We found that the membrane area increase corresponds to the lipids' peroxidation and is initiated by the delocalization of the targeted double bonds in the tails of the lipids. The subsequent decrease of membrane area can be explained by the formation of cleaved secondary products. As a result of these area changes, we observe vesicle permeabilization after a time lag that is characterized in relation with the level of unsaturation. The evolution of photosensitized vesicle radius was measured and yields an estimation of the mechanical changes of the membrane over oxidation time. The membrane is both weakened and permeabilized by the oxidation. Interestingly, the effect of unsaturation level on the dynamics of vesicles undergoing photooxidation is not trivial and thus carefully discussed. Our findings shed light on the fundamental dynamic mechanisms underlying the oxidation of lipid membranes and highlight the role of unsaturations on their physical and chemical properties.

Intracellular Monitoring of AS1411 Aptamer by Time-Resolved Microspectrofluorimetry and Fluorescence Imaging.

Time-resolved microspectrofluorimetry and fluorescence microscopy imaging-two complementary fluorescence techniques-provide important information about the intracellular distribution, level of uptake and binding/interactions inside living cell of the labeled molecule of interest. They were employed to monitor the "fate" of AS1411 aptamer labeled by ATTO 425 in human living cells. Confocal microspectrofluorimeter adapted for time-resolved intracellular fluorescence measurements by using a phase-modulation principle with homodyne data acquisition was employed to obtain emission spectra and to determine fluorescence lifetimes in U-87 MG tumor brain cells and Hs68 non-tumor foreskin cells. Acquired spectra from both the intracellular space and the reference solutions were treated to observe the aptamer localization and its interaction with biological structures inside the living cell. The emission spectra and the maximum emission wavelengths coming from the cells are practically identical, however significant lifetime lengthening was observed for tumor cell line in comparison to non-tumor one.

Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting.

Inspired by microvesicle-mediated intercellular communication, we propose a hybrid vector for magnetic drug delivery. It consists of macrophage-derived microvesicles engineered to enclose different therapeutic agents together with iron oxide nanoparticles. Here, we investigated in vitro how magnetic nanoparticles may influence the vector effectiveness in terms of drug uptake and targeting. Human macrophages were loaded with iron oxide nanoparticles and different therapeutic agents: a chemotherapeutic agent (doxorubicin), tissue-plasminogen activator (t-PA) and two photosensitizers (disulfonated tetraphenyl chlorin-TPCS2a and 5,10,15,20-tetra(m-hydroxyphenyl)chlorin-mTHPC). The hybrid cell microvesicles were magnetically responsive, readily manipulated by magnetic forces and MRI-detectable. Using photosensitizer-loaded vesicles, we showed that the uptake of microvesicles by cancer cells could be kinetically modulated and spatially controlled under magnetic field and that cancer cell death was enhanced by the magnetic targeting. From the clinical editor: In this article, the authors devised a biogenic method using macrophages to produce microvesicles containing both iron oxide and chemotherapeutic agents. They showed that the microvesicles could be manipulated by magnetic force for targeting and subsequent delivery of the drug payload against cancer cells. This smart method could provide a novel way for future fight against cancer.

Extracellular vesicles from activated platelets possess a phospholipid-rich biomolecular profile and enhance prothrombinase activity.

BACKGROUND: Extracellular vesicles (EVs), in particular those derived from activated platelets, are associated with a risk of future venous thromboembolism. OBJECTIVES: To study the biomolecular profile and function characteristics of EVs from control (unstimulated) and activated platelets. METHODS: Biomolecular profiling of single or very few (1-4) platelet-EVs (control/stimulated) was performed by Raman tweezers microspectroscopy. The effects of such EVs on the coagulation system were comprehensively studied. RESULTS: Raman tweezers microspectroscopy of platelet-EVs followed by biomolecular component analysis revealed for the first time 3 subsets of EVs: (i) protein rich, (ii) protein/lipid rich, and (iii) lipid rich. EVs from control platelets presented a heterogeneous biomolecular profile, with protein-rich EVs being the main subset (58.7% ± 3.5%). Notably, the protein-rich subset may contain a minor contribution from other extracellular particles, including protein aggregates. In contrast, EVs from activated platelets were more homogeneous, dominated by the protein/lipid-rich subset (>85%), and enriched in phospholipids. Functionally, EVs from activated platelets increased thrombin generation by 52.4% and shortened plasma coagulation time by 34.6% ± 10.0% compared with 18.6% ± 13.9% mediated by EVs from control platelets (P = .015). The increased procoagulant activity was predominantly mediated by phosphatidylserine. Detailed investigation showed that EVs from activated platelets increased the activity of the prothrombinase complex (factor Va:FXa:FII) by more than 6-fold. CONCLUSION: Our study reports a novel quantitative biomolecular characterization of platelet-EVs possessing a homogenous and phospholipid-enriched profile in response to platelet activation. Such characteristics are accompanied with an increased phosphatidylserine-dependent procoagulant activity. Further investigation of a possible role of platelet-EVs in the pathogenesis of venous thromboembolism is warranted.

Dynamics of mitochondrial membranes under photo-oxidative stress with high spatiotemporal resolution.

In our study, we harnessed an original Enhanced Speed Structured Illumination Microscopy (Fast-SIM) imaging setup to explore the dynamics of mitochondrial and inner membrane ultrastructure under specific photo-oxidation stress induced by Chlorin-e6 and light irradiation. Notably, our Fast-SIM system allowed us to observe and quantify a distinct remodeling and shortening of the mitochondrial structure after 60-80 s of irradiation. These changes were accompanied by fusion events of adjacent inner membrane cristae and global swelling of the organelle. Preceding these alterations, a larger sequence was characterized by heightened dynamics within the mitochondrial network, featuring events such as mitochondrial fission, rapid formation of tubular prolongations, and fluctuations in cristae structure. Our findings provide compelling evidence that, among enhanced-resolution microscopy techniques, Fast-SIM emerges as the most suitable approach for non-invasive dynamic studies of mitochondrial structure in living cells. For the first time, this approach allows quantitative and qualitative characterization of successive steps in the photo-induced oxidation process with sufficient spatial and temporal resolution.

Photo-dynamic induction of oxidative stress within cholesterol-containing membranes: shape transitions and permeabilization.

Photochemical internalization is a drug delivery technology employing a photo-destabilization of the endosomes and the photo-controlled release of endocyted macromolecules into the cytosol. This effect is based on the ability of some photosensitizers to interact with endosomal membranes and to photo-induce damages leading to its breakdown. The permeabilization efficiency is not quantitatively related to the importance of the damages, but to their asymmetric repartition within the leaflets. Using unilamellar vesicles and a chlorin, we studied the effect of the membrane's cholesterol content on its photo-permeabilization. First, the affinity of the chlorin for membranes was studied. Then, we asymmetrically oxidized the membranes. For DOPC/CHOL GUVs, we observed different shape transitions, in accordance with an increase followed by a decrease of the membrane effective curvature. These modifications are delayed by the cholesterol. Finally, the photo-permeabilization of GUVs occurs, corresponding to a pore formation due to the membrane tension, resulting from vesicles buddings. Cholesterol-rich GUVs permeabilization occurs after a lag, and is less important. These results are interpreted regarding both (i) the cholesterol-induced tightening of the lipids, its consequences on physical parameters of the membrane and on oxidation rate and (ii) the suggested ability of cholesterol to flip rapidly and then to relax the differential density-based stress accumulated during membrane bending.

Flavin conjugates for delivery of peptide nucleic acids.

Oligonucleotides and their analogues, such as peptide nucleic acids (PNAs), can be used in chemical strategies to artificially control gene expression. Inefficient cellular uptake and inappropriate cellular localization still remain obstacles in biological applications, however, especially for PNAs. Here we demonstrate that conjugation of PNAs to flavin resulted in efficient internalization into cells through an endocytic pathway. The flavin-PNAs exhibited antisense activity in the sub-micromolar range, in the context of a treatment facilitating endosomal escape. Increased endosomal release of flavin conjugates into the cytoplasm and/or nucleus was shown by chloroquine treatment and also--when the flavin-PNA was conjugated to rhodamine, a mild photosensitizer--upon light irradiation. In conclusion, an isoalloxazine moiety can be used as a carrier and attached to a cargo biomolecule, here a PNA, for internalization and functional cytoplasmic/nuclear delivery. Our findings could be useful for further design of PNAs and other oligonucleotide analogues as potent antisense agents.

Menstrual hygiene products: A practice evaluation.

OBJECTIVE: The choice and use of a type of hygienic protection depends on many factors. Due to growing media interest, the field of hygienic protection is evolving, however, to date no study has been carried out on this subject in France. The objective of this study was to evaluate women's practices regarding the use of hygienic protection. MATERIAL AND METHODS: From 2 June 2019 to 4 January 2020, 1,153 patients responding to a self-report questionnaire were included in a prospective, cross-sectional, observational, single-center study. The aim of the study was to describe women's practices with regard to menstrual hygiene products and the factors determining their choices, as well as their knowledge of the potential risks associated with these protections and their sources of information. RESULTS: Disposable sanitary pads were preferred by 930/1148 (81%) of patients, and menstrual tampons were used half as much (525/1150 (45.6%) of women surveyed)). The new menstrual hygiene products (washable sanitary pads, menstrual panties, and menstrual cups) were used by only 51/1150 (4.4%); 20/1149 (1.7%); 108/1150 (9.4%) of the patients; however, among the 92/1136 (8.1%) of the patients who had recently changed the type of protection, these new protections were the most popular because they were considered more ecological and less harmful to health. Menstrual hygiene products were perceived as a health risk for 924/1129 (81.8%) of patients. Menstrual toxic shock syndrome was knowledeg in only 473/1133 (41.7%) of patients. This lack of knowledge could lead to risky behavior. The majority of patients said they were not informed about hygiene protection, with only 151//1108 (13.6%) having discussed the subject with a health professional, yet 973/1067 (91.2%) wanted more information. CONCLUSION: This is the first French study on menstrual hygiene products. It showed that traditional sanitary protection was still the most widely used, but there was a growing awareness among patients about the products they used and their potential health risks as well as the consequences for the environment. Patients wanted to receive information on the subject from health professionals as well as manufacturers in order to be able to choose the product deemed the most suitable and in which they have confidence.

Hypericin incorporation and localization in fixed HeLa cells for various conditions of fixation and incubation.

Hypericin is a photosensitizer expressing high affinity for cancerous cells in vivo. Diagnosis of cancer based on hypericin fluorescence imaging has been successfully assessed in several clinical trials. Our final objective will be to evaluate the potential of hypericin fluorescence imaging to improve the efficacy of cervical cancer diagnosis performed on fixed cell smears obtained from liquid-based cytology. For this purpose, the mechanism of hypericin incorporation and localization in fixed HeLa cells using different incubation media and fixation conditions was investigated. Since the duration of fixation may play an important role, the influence of fixation time on hypericin incorporation in fixed HeLa cells was studied. The uptake and distribution of hypericin in fixed HeLa cells were found to be strongly dependent on the hypericin incubation medium: for a polar organic solvent such as the alcohol-based fixative, the localization was essentially perinuclear and nuclear; for cell culture medium supplemented with serum, the localization was cytoplasmic and non-specific; the highest incorporation was observed for the serum-free culture medium but mainly as non-fluorescent aggregates. The hypericin aggregation in the incubation medium, the passive diffusion and the partitioning between the cells and hypericin carriers seemed to be the major factors accounting for these results. The localization was found to be weakly dependent on fixation time, whereas fluctuations of hypericin fluorescence at short fixation time and stabilization after two days of fixation were observed. These results suggest that the fixed cells reached a steady state after two days of fixation.

Mitochondrial cristae modeled as an out-of-equilibrium membrane driven by a proton field.

As the places where most of the fuel of the cell, namely, ATP, is synthesized, mitochondria are crucial organelles in eukaryotic cells. The shape of the invaginations of the mitochondria inner membrane, known as a crista, has been identified as a signature of the energetic state of the organelle. However, the interplay between the rate of ATP synthesis and the crista shape remains unclear. In this work, we investigate the crista membrane deformations using a pH-dependent Helfrich model, maintained out of equilibrium by a diffusive flux of protons. This model gives rise to shape changes of a cylindrical invagination, in particular to the formation of necks between wider zones under variable, and especially oscillating, proton flux.

Magnetic resonance imaging evaluation of cervical length by the women's age: a retrospective cohort study.

OBJECTIVE: The anthropometric characteristics of the uterus evolve with pubertal development in girls. It is therefore permissible to ask until these anthropometric characteristics change, in order to know if the cervical length criterion defined for preterm delivery threats is applicable to all ages. The main objective of our study was to analyze the evolution of cervical length with the women's age outside pregnancy to overcome factors related to pregnancy that can affect cervical length. MATERIAL AND METHODS: This retrospective descriptive study over a period of 1 year from March 2017 to March 2018. The cervical length measurements were performed by Magnetic Resonnance Imaging. The cervical length was defined by sagittal T2-weighted magnetic resonance imaging (MRI) as the distance on a straight line between the external cervical os (at the point of divergence of the anterior and posterior lips) and the internal cervical os identified by an intersection between the line of the hypersignal of the glandular epithelium and a line passing through the isthmus. RESULTS: A total of 209 patients were included. The cervical length ranged from 25.2 mm on average in children under 16 years (23.6-27.1 mm) to 39.7 mm between 36 and 40 years (27.9 -58.9 mm). There was a linear association between age and cervical length, irrespective of maternal anthropometric data (Pearson's coefficient ρ = 0.43, 95% CI 0.32-0.54 (p < 0.01). In multivariate analysis, the only factors associated with cervical length were women's age (p < 0.01) and the prior delivery (p < 0.01). CONCLUSION: The cervical length is correlated with women age and the prior delivery.

Asymmetric oxidation of giant vesicles triggers curvature-associated shape transition and permeabilization.

Oxidation of unsaturated lipids is a fundamental process involved in cell bioenergetics as well as in cell death. Using giant unilamellar vesicles and a chlorin photosensitizer, we asymmetrically oxidized the outer or inner monolayers of lipid membranes. We observed different shape transitions such as oblate to prolate and budding, which are typical of membrane curvature modifications. The asymmetry of the shape transitions is in accordance with a lowered effective spontaneous curvature of the leaflet being targeted. We interpret this effect as a decrease in the preferred area of the targeted leaflet compared to the other, due to the secondary products of oxidation (cleaved-lipids). Permeabilization of giant vesicles by light-induced oxidation is observed after a lag and is characterized in relation with the photosensitizer concentration. We interpret permeabilization as the opening of a pore above a critical membrane tension, resulting from the budding of vesicles. The evolution of photosensitized giant vesicle lysis tension was measured and yields an estimation of the effective spontaneous curvature at lysis. Additionally photo-oxidation was shown to be fusogenic.

Membrane deformation under local pH gradient: mimicking mitochondrial cristae dynamics.

Mitochondria are cell substructures (organelles) critical for cell life, because biological fuel production, the ATP synthesis by oxidative phosphorylation, occurs in them driven by acidity (pH) gradients. Mitochondria play a key role as well in the cell death and in various fatigue and exercise intolerance syndromes. It is clear now that mitochondria present an astonishing variety of inner membrane morphologies, dynamically correlated with their functional state, coupled with the rate of the ATP synthesis, and characteristic for normal as well as for pathological cases. Our work offers some original insights into the factors that determine the dynamical tubular structures of the inner membrane cristae. We show the possibility to induce, by localized proton flow, a macroscopic cristae-like shape remodeling of an only-lipid membrane. We designed a minimal membrane system (GUV) and experimentally showed that the directional modulation of local pH gradient at membrane level of cardiolipin-containing vesicles induces dynamic cristae-like membrane invaginations. We propose a mechanism and theoretical model to explain the observed tubular membrane morphology and suggest the underlying role of cardiolipin. Our results support the hypothesis of localized bioenergetic transduction and contribute to showing the inherent capacity of cristae morphology to become self-maintaining and to optimize the ATP synthesis.

Cellular uptake and subcellular distribution of chlorin e6 as functions of pH and interactions with membranes and lipoproteins.

The uptake and more importantly the subcellular distribution of photosensitizers are major determinants of their efficacy. In this paper, the cellular internalization of chlorin e6 (Ce6), a photosensitizer bearing three carboxylic chains, is considered with emphasize on pH effects. Small unilamellar vesicles are used as models to investigate the dynamics of interactions of Ce6 with membranes. The entrance and exit steps from the outer lipid hemileaflet are very fast (~ms). A slow transfer of Ce6 through the membrane was observed only for thin bilayers made of dimyristoleoyl-phosphatidylcholine. Ce6 did not permeate through bilayers consisting of longer phospholipids more representative of biological membranes. These results along with previous data on the interactions of Ce6 with low-density lipoproteins (LDL) are correlated with cellular studies. After 15 min incubation of HS68 human fibroblasts with Ce6, fluorescence microscopy revealed labeling of the plasma membrane and cytosolic vesicles different from lysosomes. When vectorized by LDL, Ce6 was mainly localized in lysosomes but absent from the plasma membrane. Internalization of LDL bound photosensitizer via ApoB/E receptor mediated pathway was demonstrated by overexpression experiments. A pH decrease from 7.4 to 6.9 did not affect the intracellular distribution of Ce6, but significantly increased its overall cellular uptake.

The pH-dependent distribution of the photosensitizer chlorin e6 among plasma proteins and membranes: a physico-chemical approach.

Decrease in interstitial pH of the tumor stroma and over-expression of low density lipoprotein (LDL) receptors by several types of neoplastic cells have been suggested to be important determinants of selective retention of photosensitizers by proliferative tissues. The interactions of chlorin e6 (Ce6), a photosensitizer bearing three carboxylic groups, with plasma proteins and DOPC unilamellar vesicles are investigated by fluorescence spectroscopy. The binding constant to liposomes, with reference to the DOPC concentration, is 6 x 10(3) M(-1) at pH 7.4. Binding of Ce6 to LDL involves about ten high affinity sites close to the apoprotein and some solubilization in the lipid compartment. The overall association constant is 5.7 x 10(7) M(-1) at pH 7.4. Human serum albumin (HSA) is the major carrier (association constant 1.8 x 10(8) M(-1) at pH 7.4). Whereas the affinity of Ce6 for LDL and liposomes increases at lower pH, it decreases for albumin. Between pH 7.4 and 6.5, the relative affinities of Ce6 for LDL versus HSA, and for membranes versus HSA, are multiplied by 4.6 and 3.5, respectively. These effects are likely driven by the ionization equilibria of the photosensitizer carboxylic chains. Then, the cellular uptake of chlorin e6 may be facilitated by its pH-mediated redistribution within the tumor stroma.

Tetrapyrrole-photosensitizers vectorization and plasma LDL: a physico-chemical approach.

A photosensitizer is defined as a chemical entity able to induce, under light-irradiation effect, a chemical or physical alteration of another chemical entity. Thanks to their preferential retention in proliferating tissues, some photosensitizers are therapeutically used such as in photodynamic therapy (PDT). Besides, this method has already been approved for several indications. The selectivity of photosenzitizers for cells in proliferation involves both their association with low density lipoproteins (LDLs) and their ability to cross membranes under various pH conditions. The photosensitizers used are in most cases based on the porphyrin structure, but other compounds, of which far-red-light absorption properties are most compatible with biological tissues irradiation, have been developed, such as phthalocyanines. This paper presents physico-chemical studies of the interaction of a disulfonated aluminium phthalocyanine (AlPcS2) with human LDLs. The data obtained are compared with the parameters of the interaction of these lipoproteins with deuteroporphyrin (DP) and chlorin e6 (Ce6). A close attention is paid to the dynamic aspects of these phenomena. The data obtained on these simple systems then allowed us to interpret the sub-cellular localization of the photosensitizers on a human line of fibroblasts, and to evaluate the influence of LDLs on the intracellular distribution of the compounds. This last point is of major importance because the localization of such photosensitizers (in particular AlPcS2) in endocytic vesicles and their subsequent ability to induce a release of the contents of these vesicles - including externally added macromolecules - into the cytosol is the basis for a recent method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules. The comprehension of the mechanisms governing this particular sub-cellular localization could allow the design of better candidates for PCI.

Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins.

Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake.

Dynamics of pH-dependent self-association and membrane binding of a dicarboxylic porphyrin: a study with small unilamellar vesicles.

Steady-state and stopped-flow measurements of the absorbance and fluorescence of aqueous solutions were performed to characterize the pH-dependent ionization and aggregation states of deuteroporphyrin. Porphyrin self-association promoted by neutralization of the carboxylic groups takes place within a few milliseconds impeding characterization of the monomer ionization states. Extrapolation at infinite dilution of the values obtained from steady-state measurements yielded the pKs of the carboxylic groups (6.6, 5.3) and inner nitrogens (4.1, 2.3). The kinetics of interactions of the porphyrin with unilamellar fluid state dioleoylphosphatidylcholine vesicles was examined in a large pH range, with focus on the entry step. From alkaline pH to a value of 6.5, the entrance rate is maximal (1.69 x 10(6) M(-1) s(-1) versus phospholipid concentration). It decreases to 2.07 x 10(5) M(-1) s(-1) at lower pH with an apparent pK of 5.39. This effect appears to be related to the formation of porphyrin dimer rather than to the protonation of inner nitrogen. In keeping with previous data, these results support the concept of a pH-mediated selectivity of carboxylic porphyrins for tumor. They also indicate that the propensity of these molecules to self-associate at low pH could yield to some retention in acidic intracellular vesicles of the endosome/lysosome compartment.

Release kinetics of an amphiphilic photosensitizer by block-polymer nanoparticles.

Block-polymer nanoparticles are now well-known candidates for the delivery of various non-soluble drugs to cells. The release of drugs from these nanoparticles is a major concern related to their efficiency as nanovectors and is still not completely deciphered. Various processes have been identified, depending of both the nature of the block-polymer and those of the drugs used. We focused our interest on an amphiphilic photosensitizer studied for photodynamic treatments of cancer, Pheophorbide-a (Pheo). We studied the transfer of Pheo from poly(ethyleneglycol-b-ϵ-caprolactone) nanoparticles (I) to MCF-7 cancer cells and (II) to models of membranes. Altogether, our results suggest that the delivery of the major part of the Pheo by the nanoparticles occurs via a direct transfer of Pheo from the nanoparticles to the membrane, by collision. A minor process may involve the internalization of a small amount of the nanoplatforms by the cells. So, this research illustrates the great care necessary to address the question of the choice of such nanocarriers, in relation with the properties - in particular the relative hydrophobicity - of the drugs encapsulated, and gives elements to predict the mechanism and the efficiency of the delivery.