Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): S. Vaz, R. Silva, M.H. Amaral, E. Martins, J.M. Sousa Lobo, A.C. Silva

l-Ascorbic acid alkyl esters action on stratum corneum model membranes: An insight into the mechanism for enhanced skin permeation Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Yenisleidy de las Mercedes Zulueta Díaz, Karen Menghi, Maria Laura Guerrero, Natalia Nocelli, María Laura Fanani Abstract L-ascorbic acid alkyl esters (ASCn) are lipophilic forms of vitamin C, which act as skin permeation enhancers. We investigated the physical changes induced by incorporating ASCn into stratum corneum (SC) lipid membranes and correlated this with the mechanism proposed in the literature for skin permeation enhancement phenomena. We used lipid monolayers to explore the 2D structure and elasticity of the lipid-enhancer systems. As a comparison, the classic permeation enhancer, oleic acid (OA) and the non-enhancer analogue stearic acid (SA) were analysed. The incorporation of ASCn or OA into SC membranes resulted in more liquid-like films, with a dose-dependent lowering of the compressibility modulus. Brewster angle microscopy (BAM) evidenced partial miscibility of the enhancer with SC lipid components, stabilising the liquid-expanded phase. At the nanoscale, AFM showed that SC lipids form heterogeneous membranes, which underwent structural alterations after incorporating ASCn and fatty acids, such as SA and OA. The lower, cholesterol-enriched phase appears to concentrate the enhancers, whilst the higher ceramide-enriched phase concentrated the non-enhancer SA. Our results and previously reported pieces of evidence indicate a strong pattern in which the rheological properties of SC lipid films are determinant for skin permeation phenomena. Graphical abstract

Doxorubicin-doxorubicin conjugate prodrug as drug self-delivery system for intracellular pH-triggered slow release Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Jiagen Li, Xinming Li, Peng Liu Abstract Drug content and releasing rate are the main determining factors for the drug delivery systems (DDSs). Here, doxorubicin dimer (D-DOXcar) was synthesized as drug-drug conjugate prodrug with high drug content of 86%, via an acid-triggered hydrolysable carbamate linker. The prodrug nanoparticles (D-DOXcar-NP) with different diameters were prepared as drug self-delivery system (DSDS) for intracellular pH-triggered slow release. They showed size- and concentration-dependent pH-triggered slow DOX release. For the D-DOXcar-sNP with smaller diameter, the cumulative release ratio reached 25.6% at pH 5.0 within 60 h. The MTT results demonstrated that the proposed DSDS showed similar tumor inhibition regardless of carboxylesterases, and an enhanced anti-tumor efficacy on the HepG2 cells in comparison with the free DOX. Graphical abstract

Dual function of interleukin-23 Aptamer to suppress brain inflammation via attachment to macrophage stimulating 1 kinase and interleukin-23 Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Hossein Shahdadi Sardou, Ali Jebali, Maryam Iman Abstract In the present study, the dual function of interleukin-23 (IL-23) Aptamer to suppress brain inflammation via attachment to macrophage stimulating 1 (MST1) kinase and IL-23, was introduced. Also, the anti-inflammatory property of IL-23 Aptamer has been investigated. This study showed that IL-23 Aptamer could reduce the clinical development of brain inflammation induced by Parathion, as an important organophosphate toxin. Both immunostaining and H&E staining indicated that the total inflammatory infiltration foci were remarkably decreased in IL-23 Aptamer-treated mice. Moreover, this study showed that IL-23 Aptamer reduced both absolute and relative numbers of MST1+CD4 + Th1 cells and IL-23-producing cells. Analysis of the Hippo signaling genes showed a sharp decrease of MST1 kinase compared with other genes (P < 0.001). Moreover, computer-assisted molecular docking demonstrated that both MST1 kinase and IL-23 could tightly attach to IL-23 Aptamer, and maybe block it. Taken together, IL-23 Aptamer coud decrease brain inflammation via suppressing MST1 kinase and IL-23. Graphical abstract

Yttrium vanadates based ratiometric fluorescence probe for alkaline phosphatase activity sensing Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Wei Xiao, Fang Liu, Gen-Ping Yan, Wei-Guo Shi, Kang-liang Peng, Xue-qing Yang, Xiao-jing Li, Hou-chuan Yu, Zhi-ying Shi, Hui-Hui Zeng Abstract Alkaline phosphatase (ALP) is an important biomarker for diagnosis, and the abnormal level of serum ALP is closely related to a variety of diseases. In present work, a ratiometric fluorescence probe based on hybrid nanoparticles CDs@YVO4: Dy3+ nanoparticle is introduced for alkaline phosphatase (ALP) activity determination. The CDs@YVO4: Dy3+ probe is constructed by the carbon dots (CDs) and YVO4: Dy3+ through a simple mixing method, in which the blue emission of CDs at 405 nm acts as the calibrated signal, the green emission of YVO4: Dy3+ at 574 nm decreased with the increasing targets ALP, and used as the output signal. In addition, the Cu2+ and pyrophosphate (PPi) were also employed in this strategy to utilize the excellent fluorescnece quenching efficiency of Cu2+ to the Dy3+ ions emission of CDs@YVO4: Dy3+, as well as the strong affinity of PPi for Cu2+. In the presence of analyts ALP, ALP catalyzes the hydrolysis of PPi, causing the release of Cu2+, resulting in the Dy3+ ions emission quenched, while the CDs emission at 405 nm retained unchanged, based on this, we designed the off-on-off ratiometric fluorescence platform for ALP sensing. The experiment result shows that the ratio of F574/F405 is linear to the concentration of ALP in arange of 0.05∼3000 U/L with a detection limit of 0.04 U/L, which is comparable or better than those reported fluorescence probe, especially the calibrated signal introduction of CDs can eliminate the background interference, improve the accuracy of proposed probe greatly. Furthermore, the discrimination of ALP enzyme inhibitor with the IC50 of 26 μM, and ALP concentration in real human serum sample has also demonstrated the applicability of CDs@YVO4: Dy3+ fluorescence sensor well. Graphical abstract

A 1,8-naphthalimide-[12]aneN3 derivative for efficient Cu2+ recognition, lysosome staining and siRNA delivery Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Yong-Guang Gao, Kai Dang, Wen-Juan Zhang, Fen-Li Liu, Suryaji Patil, Abdul Qadir, Ai-Xiang Ding, Ai-Rong Qian Abstract Development of multifunctional compounds as both fluorescence probes and non-viral vectors is still difficult till date. It is necessary to overcome many hurdles such as the balance of hydrophilic and hydrophobic moieties, binding affinity between multifunctional compound and targeting substrate, the cytotoxicity of multifunctional compound, and so on. In this work, the performances of compound 1 on Cu2+ recognition, lysosome staining and siRNA (small interfering RNA) delivery were investigated. It was found that compound 1 exhibited high selectivity and sensitivity toward Cu2+ in aqueous solutions. The fluorescence emission of 1 was quenched by a factor of 42-fold in the presence of Cu2+ ions. Even in the common pure organic solutions, still more than 8-fold fluorescence quenching was achieved. Due to its high sensitivity to the pH, the complex of 1-Cu was also successfully applied in selective staining of lysosome in HeLa cells. Furthermore, cellular uptake experiment revealed that compound 1 showed good RNA delivery ability in HeLa, HepG2, U2Os and MC3T3-E1 cells, and its performance was better than commercial agents lipofectamine 2000 and 25 kDa PEI (Polyethylenimine). The RNA interference effect mediated by compound 1 was further evaluated by real-time fluorescent quantitative PCR experiment. Compound 1 showed much higher transfection efficacy than lipofectamine 2000 in MC3T3-E1 cells. Our study demonstrated that 1,8-naphthalimide- [12]aneN3 compound 1 with low cytotoxicity, high specificity towards Cu2+ and lysosome, high transfection efficacy, and low cost is an efficient multifunctional material both in molecular recognition and gene delivery. Graphical abstract

Significant bile salt induced perturbation of niosome membrane: A molecular level interaction study using 1-Naphthol fluorescence Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Jhili Mishra, Ashok Kumar Mishra Abstract This study demonstrates that significant perturbation of tween20:cholesterol(1:1) niosome membrane takes place even at premicellar concentration of bile salts. Here, 1-naphthol (1-NpOH), a known and sensitive excited state proton transfer (ESPT) probe, was used to understand the nature of perturbation of the membrane in an unbuffered medium. The significant decrease in 1-NpOH fluorescence intensity in niosome-bile salt mixed system at both lower (10 °C) and higher (50 °C) temperatures indicates the bile salts [sodium cholate (NaC) and sodium deoxycholate (NaDC)] induce perturbation of niosome membranes. Variations in the fluorescence lifetime values of both the prototropic emissions (neutral and anionic species) along with the proton transfer rate of 1-NpOH confirm the bile salts perturb up to the hydrophobic core domain of the niosomal membranes. Bile salts induce size change of the niosomal membrane is confirmed through dynamic light scattering study. Graphical abstract Effect of premicellar concentration of Bile salts on TW20:cholesterol(1:1) niosome membrane

Biomedical application of graphene: From drug delivery, tumor therapy, to theranostics Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Saijie Song, He Shen, Yuli Wang, Xiaohong Chu, Jing Xie, Ninglin Zhou, Jian Shen Abstract The rise of graphene has driven great revolution in various fields, e. g. electronics, device, energy, etc., owing to the well-researched understanding of its physical and chemical properties. In the very recent decade, scientists have poured significant efforts to explore the biological functions of graphene and expand its biomedical applications, including drug delivery, tumor therapy, and theranostics. Encouraged by the inspiring research results and promising contributions of graphene to biomedicine field, herein, we systematically summarize the recent advance of graphene for biomedical application. In this review, we introduce the development of graphene in biomedicine, from drug delivery, tumor therapy, to theranostics. We also demonstrate the surface engineering and multifunctional modification of graphene, and further present the active role of rational decoration in drug delivery, therapy, and theranostic application. In detail, we summarize the surface engineering, active-targeting modification, stimuli-responsive decoration, and their application in anticancer drugs delivery, multiple therapeutic approach, dual-model imaging guided therapy. On the basis of the systematic summary, in the final, we further present the development tendency of graphene in biomedicine, aiming to provide some valuable guidelines for further research. Graphical abstract

Gallic acid loaded poloxamer gel as new adjuvant strategy for melanoma: A preliminary study Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Maddalena Sguizzato, Giuseppe Valacchi, Alessandra Pecorelli, Paola Boldrini, Fanny Simelière, Nicolas Huang, Rita Cortesi, Elisabetta Esposito Abstract The present study describes the production and characterization of poloxamer gels containing the antioxidant molecule gallic acid. The gels were particularly designed in order to obtain a formulation suitable for administration on the skin to treat melanoma. The polymer concentration was selected after rheological characterization and determination of gel transition temperature. In order to study the gallic acid diffusion, in vitro experiments were performed using Franz cells associated to different membranes. As first approach the gallic acid diffusion was evaluated through synthetic membranes, such as cellulose, nylon, polycarbonate, polytetrafluoroethylene, polyvinylidene fluoride and the commercial Strat-M® membrane. The membranes were employed separately or in association and compared to stratum corneum epidermis membranes, in order to find a system able to reproduce the gallic acid diffusion through the skin. Selected membranes were used for studying gallic acid diffusion from poloxamer gel. It was found that the diffusion of gallic acid was dramatically influenced by the type of membrane, both in the case of the aqueous solution or poloxamer gel. Scratch wound healing and migration assays conducted on human keratinocytes and melanoma cells demonstrated the ability of gallic acid loaded gel to inhibit cellular migration, suggesting its potential as adjuvant strategy for melanoma. Graphical abstract

Kinetic study of Aβ(1-42) amyloidosis in the presence of ganglioside-containing vesicles Publication date: 1 January 2020 Source: Colloids and Surfaces B: Biointerfaces, Volume 185 Author(s): Yanping Dai, Mingxi Zhang, Xiulei Shi, Kang Wang, Guanbin Gao, Lei Shen, Taolei Sun Abstract Alzheimer's disease (AD) is characterized by the amyloid-beta peptide (Aβ) misfolding to form aberrant amyloid aggregates in the brain. Although recent evidence implicates that amyloid deposition in vivo is highly related to biomembranes, how the characteristic lipid components of neuronal membranes mediate this process remains to be fully elucidated. Herein, we established vesicle models to mimic exosomes and investigated their influence on the kinetics of Aβ(1-42) amyloidosis. By using ternary vesicles composed of three brain lipids monosialoganglioside GM1, cholesterol and sphingomyelin, we found that GM1 could regulate peptide fibrillation by facilitating the conformational transition of Aβ(1-42), and further quantitatively analyzed the influence of GM1-containing vesicles on the kinetics of Aβ(1-42) fibrillation. In addition, GM1-containing vesicles induced the formation of Aβ(1-42) fibrils at low concentrations, and these fibrils were toxic to PC12 cells. By analyzing the role of GM1 in this ternary mixture of membranes at the molecular level, we confirmed that GM1 clusters are presented as attachment sites for peptides, thus promoting the fibrillation of Aβ(1-42). Graphical abstract