In this report we describe the fabrication and characterization of a phospholipid/alkanethiol hybrid bilayer membrane in air. The bilayer is formed by the interaction of phospholipid with the hydrophobic surface of a self-assembled alkanethiol monolayer on gold. We have characterized the resulting hybrid bilayer membrane in air using atomic force microscopy, spectroscopic ellipsometry, and reflection-absorption infrared spectroscopy. These analyses indicate that the phospholipid added is one monolayer thick, is continuous, and exhibits molecular order which is similar to that observed for phospholipid/phospholipid model membranes. The hybrid bilayer prepared in air has also been re-introduced to water and characterized using neutron reflectivity and impedance spectroscopy. Impedance data indicate that when moved from air to water, hybrid bilayers exhibit a dielectric constant and thickness that is essentially equivalent to hybrid bilayers prepared in situ by adding phospholipid vesicles to alkanethiol monolayers in water. Neutron scattering from these samples was collected out to a wave vector transfer of 0.25 A(-1), and provided a sensitivity to changes in total layer thickness on the order of 1-2 A. The data confirm that the acyl chain region of the phospholipid layer is consistent with that observed for phospholipid-phospholipid bilayers, but suggest greater hydration of the phospholipid headgroups of HBMs than has been reported in studies of lipid multilayers.
Plasmid DNA molecules with unique loop structures have widespread bioapplications, in many cases relying heavily on delivery vehicles to introduce them into cells and achieve their functions. Herein, we demonstrate that control over delicate nanotopography of silica nanoparticles as plasmid DNA vectors has significant impact on the transfection efficacy. For silica nanoparticles with rambutan-, raspberry-, and flower-like morphologies composed of spike-, hemisphere-, and bowl-type subunit nanotopographies, respectively, the rambutan-like nanoparticles with spiky surfaces demonstrate the highest plasmid DNA binding capability and transfection efficacy of 88%, higher than those reported for silica-based nanovectors. Moreover, it is shown that the surface spikes of rambutan nanoparticles provide a continuous open space to bind DNA chains via multivalent interactions and protect the gene molecules sheltered in the spiky layer against nuclease degradation, exhibiting no significant transfection decay. This unique protection feature is in great contrast to a commercial transfection agent with similar transfection performance but poor protection capability against enzymatic cleavage. Our study provides new understandings in the rational design of nonviral vectors for efficient gene delivery.
Iron oxide nanoparticles (IONPs) have emerging anti-cancer applications via polarizing tumor-associated macrophages from tumor-promoting phenotype (M2) to tumor-suppressing phenotype (M1). However, the underlying mechanism and structure-function relationship remain unclear. We report magnetite IONPs are more effective compared to hematite in M1 polarization and tumor suppression. Moreover, magnetite IONPs specifically rely on interferon regulatory factor 5 signaling pathway for M1 polarization and downregulate M2-assoicated arginase-1. This study provides new understandings and paves the way for designing advanced iron-based anti-cancer technologies.
Non‐invasive cancer photothermal therapy (PTT) is a promising replacement for traditional cancer treatments. The second near‐infrared region induced PTT (NIR‐II PTT, 1000–1500 nm) with less energy dissipation has been developed for deeper‐seated tumor treatment in recent years compared with the traditional first near‐infrared light (750–1000 nm). In addition, the use of emerging inorganic 2D nanomaterials as photothermal agents (PTAs) further enhanced PTT efficiency due to their intrinsic photothermal properties. NIR‐II light stimulated inorganic 2D nanomaterials for PTT is becoming a hot topic in both academic and clinical fields. This review summarizes the categories, structures, and photothermal conversion properties of inorganic 2D nanomaterials for the first time. The recent synergistic strategies of NIR‐II responsive PTT combined with other treatment approaches including chemotherapy, chemodynamic therapy, photodynamic therapy, radiotherapy are summarized. The future challenges and perspectives on these 2D nanomaterials for NIR‐II responsive PTT systems construction are further discussed.
In 1974, Gehring posed the problem of minimizing the length of two linked curves separated by unit distance. This constraint can be viewed as a measure of thickness for links, and the ratio of length over thickness as the ropelength. In this paper we refine Gehring's problem to deal with links in a fixed link-homotopy class: we prove ropelength minimizers exist and introduce a theory of ropelength criticality. Our balance criterion is a set of necessary and sufficient conditions for criticality, based on a strengthened, infinite-dimensional version (Theorem 5.4) of the Kuhn-Tucker theorem. We use this to prove that every critical link is C 1 with finite total curvature. The balance criterion also allows us to explicitly describe critical configurations (and presumed minimizers) for many links including the Borromean rings. We also exhibit a surprising critical configuration for two clasped ropes: near their tips the curvature is unbounded and a small gap appears between the two components. These examples reveal the depth and richness hidden in Gehring's problem and our natural extension. 57M25; 49Q10, 53A04
The direct depletion of lactate accumulated in the tumor microenvironment holds promise for cancer therapybut remains challenging.H erein, we report ao ne-pot synthesis of openwork@ dendritic mesoporous silica nanoparticles (ODMSNs) to address this problem. ODMSNs self-assembled through atime-resolved lamellar growth mechanism feature an openworked core and ad endritic shell, both constructed by silica nanosheets of % 3nm. With alarge pore size, high surface area and pore volume,O DMSNs exhibited ah igh loading capacity (> 0.7 gg À1)o fl actate oxidase (LOX) and enabled intratumoral lactate depletion by > 99.9 %, leading to antiangiogenesis,d own-regulation of vascular endothelial growth factor,and increased tumor hypoxia. The latter event facilitates the activation of ac o-delivered prodrug for enhancing antitumor and anti-metastasis efficacy.T his study provides an innovative nano-delivery system and demonstrates the first example of direct lactate-depletion-enabled chemotherapy.
Hypoxia-activated prodrugs have brought new opportunities for safe and effective tumor ablation, but their therapeutic efficacy is limited by insufficient activation in tumor microenvironments. Herein, a novel cascade delivery system with tandem functions by integrating a hypoxia-activated prodrug (AQ4N) and glucose oxidase (GOx) is designed to improve its efficacy. Innovative yolk-shell organosilica nanoparticles with a tetrasulfide bridged composition, a small-pore yolk, and a large-pore shell featuring a shell-to-yolk stepwise degradability are constructed as a carrier for AQ4N and GOx, one enzyme that catalyzes the oxidation of glucose to produce hydrogen peroxide. The glutathione (GSH) is depleted by tetrasulfide bond in the framework and induces shell degradation for fast release of GOx, which in turn induces starvation (glucose removal), oxidative cytotoxicity (H 2 O 2 production and GSH depletion), and hypoxia (oxygen consumption). Finally, the hypoxia activates the liberated prodrug AQ4N for chemotherapy. The cascading and synergistic functions including GSH depletion, starvation, oxidative cytotoxicity, and chemotherapy lead to improved performance in tumor inhibition and antimetastasis.
Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death and activating immune cells. A simple physical mixture of nanoreactors and chemodrugs in combination with immune checkpoint blockades show synergistically and concurrently enhanced chemo-immunotherapy efficacy, inhibiting the growth of both treated primary immunosuppressive tumors and untreated distant tumors. The off-the-shelf strategy uses tumor antigens generated in situ and avoids cargo loading, and is thus a substantial advance in personalized nanomedicine for clinical translation.
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