Cholesterol-like Condensing Effect of Perfluoroalkyl Substances on a Phospholipid Bilayer

Shen, Zhiqiang; Ge, Q. J.; Ye, Huilin; Tang, Shan; Liu, Ying

doi:10.1021/acs.jpcb.0c00980

Cited by 17 publications

(11 citation statements)

References 64 publications

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“…37 The data confirmed that even as a micelle core, the Fn had a considerable impact on the fluoroamphiphiles' biointeractions. Previous studies showed that the fluorocarbons and fluoroamphiphiles could exert a "cholesterol-like" condensing effect on the lipid bilayer/ membrane, 38,39 allowing to orient the lipids' polar head groups toward the fluoroamphiphiles. This unique property might facilitate the interaction of the PEGm-Fn with cell membrane (Figures 2D and S2), to trigger the efficient cellular uptake (Figures 1H,I and 2A).…”

Section: Resultsmentioning

confidence: 99%

Potential-Independent Intracellular Drug Delivery and Mitochondrial Targeting

Liu

Zhang

et al. 2021

ACS Nano

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In this study, two types of the fluoroamphiphile analogs were synthesized and self-assembled into the “core–shell” micellar nanocarriers for intracellular delivery and organelle targeting. Using the fluorescent dyes or vitamin E succinate as the cargo, the drug delivery and targeting capabilities of the fluoroamphiphiles and their micelles were evaluated in the cell lines, tumor cell spheroids, and tumor-bearing mice. The “core-fluorinated” micelles exhibited favorable physicochemical properties and improved the cellular uptake of the cargo by around 20 times compared to their “shell-fluorinated” counterparts. The results also indicated that the core-fluorinated micelles underwent an efficient clathrin-mediated endocytosis and a rapid endosomal escape thereafter. Interestingly, the internalized fluoroamphiphile micelles preferentially accumulated in mitochondria, by which the efficacy of the loaded vitamin E succinate was boosted both in vitro and in vivo. Unlike the popularly used cationic mitochondrial targeting ligands, as a charge-neutral nanocarrier, the fluoroamphiphiles’ mitochondrial targeting was potential independent. The mechanism study suggested that the strong binding affinity with the phospholipids, particularly the cardiolipin, played an important role in the fluoroamphiphiles’ mitochondrial targeting. These charge-neutral fluoroamphiphiles might have great potential to be a simple and reliable tool for intracellular drug delivery and mitochondrial targeting.

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Section: Resultsmentioning

confidence: 99%

Potential-Independent Intracellular Drug Delivery and Mitochondrial Targeting

Liu

Zhang

et al. 2021

ACS Nano

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“…Antiseptic Picloxydine, Octenidine, Miramistin [470], Polyhexamethylene Biguanide [471] Insecticide Parathione [132], Fipronil [472], Dibutyl succinate [203] Former Drugs d-sotalol, cisapride [473], piracetam (status varies among countries) [474], ORG-12962 [199] Toxic xenobiotic Polybrominated-diphenyl-ethers [475], Bisphenol [476], Perfluoroalkyls [477], nitroaromatic explosives (TNT,2A, and 24DA) [478][479][480][481], 1,4-Dioxane [482], Benzo[a]pyrene [483] Nanomaterials Graphene [484][485][486][487], Carbon Dots [488], Phosphorene Oxide Nanosheets [489], Gold Nanoparticles [490][491][492], Titanium Dioxide Nanoparticles [493], Generic Nanoparticles (coarse grained) [494], Fullerene [495][496][497][498], Previous reviews [499] Polymers Poly(ethyleneoxide)-Poly-(propylene oxide) [500], polyethylenimine [501], Poloxamer [502,503], Pluronics [504,505], poly(ethyleneglycol)-desferrioxamine/ gallium [506], PEG functionalized with carbochydrates [507] and peptides…”

Section: Application Xenobioticmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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“…PFASs have similar structures to fatty acids, and the binding between PFASs and proteins might interfere with glycolipid metabolism . Molecular dynamics simulations have also suggested that PFOA, PFNA, PFOS, and PFHxS can penetrate the lipid bilayer . In the present study, multiple linear regression models were used to explore associations between PFASs and serum lipid parameters.…”

Section: Resultsmentioning

confidence: 98%

“…50 Molecular dynamics simulations have also suggested that PFOA, PFNA, PFOS, and PFHxS can penetrate the lipid bilayer. 51 In the present study, multiple linear regression models were used to explore associations between PFASs and serum lipid parameters. Significant positive associations were found between most PFASs (including PFNA, PFDA, PFUnDA, PFOS, and C8 Cl-PFESA) and CHOL, TL, and LDL-C (Table S11).…”

Section: Resultsmentioning

confidence: 99%

Associations between Novel and Legacy Per- and Polyfluoroalkyl Substances in Human Serum and Thyroid Cancer: A Case and Healthy Population in Shandong Province, East China

Liu

Zhang

Meng

et al. 2021

Environ. Sci. Technol.

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Per- and polyfluoroalkyl substances (PFASs) are widely detected in the environment and may cause adverse human health effects after exposure. Studies on the effect of PFASs on some health end points, including cancer, are still limited and show inconsistent results. In this research, 319 participants were recruited from Shandong Province, East China, consisting of patients with thyroid cancer and healthy controls. Seven novel and legacy PFASs were frequently detected (detection rate > 75%) in the serum samples of the participants. The concentrations of perfluorooctanoic acid (PFOA) were the highest in the case and control groups. Males showed significantly higher concentrations of PFASs than females. Exposure to PFASs was inversely associated with the risk of thyroid cancer. In the control group, we identified significant positive associations between PFASs and free thyroxine (FT4) as well as between PFOA and thyroid stimulating hormone (TSH) in females. A significant negative association between perfluorononanoic acid (PFNA) and triiodothyronine (T3) was observed in males. Our results suggest that exposure to certain PFASs could interfere with thyroid function. To our knowledge, this is the first case–control study demonstrating associations between novel and legacy PFASs in human and thyroid cancer.

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Cholesterol-like Condensing Effect of Perfluoroalkyl Substances on a Phospholipid Bilayer

Cited by 17 publications

References 64 publications

Potential-Independent Intracellular Drug Delivery and Mitochondrial Targeting

Potential-Independent Intracellular Drug Delivery and Mitochondrial Targeting

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Associations between Novel and Legacy Per- and Polyfluoroalkyl Substances in Human Serum and Thyroid Cancer: A Case and Healthy Population in Shandong Province, East China

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