Gene/Protein Disease Symptom Drug Enzyme Compound
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Melanoma skin cancer is one of the most dangerous skin cancers and the main cause of skin-cancer-related mortality. Hyaluronic acid (HA) has been used as an effective transdermal delivery carrier of chemical drugs and biopharmaceuticals. In this work, a nanographene oxide-HA conjugate (NGO-HA) was synthesized for photothermal ablation therapy of melanoma skin cancer using a near-infrared (NIR) laser. Confocal microscopy and ex vivo bioimaging clearly visualized the remarkable transdermal delivery of NGO-HA to tumor tissues in the skin of mice, which might be ascribed to highly expressed HA receptors and relatively leaky structures around tumor tissues, enabling the enhanced permeation and retention of nanoparticles. The NIR irradiation resulted in complete ablation of tumor tissues with no recurrence of tumorigenesis. The antitumor effect was confirmed by ELISA for caspase-3 activity and histological and immunohistochemical analyses with TUNEL assay for tumor apoptosis. Taken together, we could confirm the feasibility of transdermal NGO-HA for photothermal ablation therapy of melanoma skin cancers.
ACS Nano 2014 Jan 28
PMID:Nanographene oxide-hyaluronic acid conjugate for photothermal ablation therapy of skin cancer. 2438 90

Structure-property relationships are of fundamental importance to develop quantitative models describing charge transport in organic semiconductor based electronic devices, which are among the best candidates for future portable and lightweight electronic applications. While microstructural investigations, such as those based on X-rays, electron microscopy, or polarized optical probes, provide necessary information for the rationalization of transport in macromolecular solids, a general model predicting how charge accommodates within structural maps is not yet available. Therefore, techniques capable of directly monitoring how charge is distributed when injected into a polymer film and how it correlates to structural domains can help fill this gap. Supported by density functional theory calculations, here we show that polarized charge modulation microscopy (p-CMM) can unambiguously and selectively map the orientational order of the only conjugated segments that are probed by mobile charge in the few nanometer thick accumulation layer of a high-mobility polymer-based field-effect transistor . Depending on the specific solvent-induced microstructure within the accumulation layer, we show that p-CMM can image charge-probed domains that extend from submicrometer to tens of micrometers size, with markedly different degrees of alignment. Wider and more ordered p-CMM domains are associated with improved carrier mobility, as extracted from device characteristics. This observation evidences the unprecedented opportunity to correlate, directly in a working device, electronic properties with structural information on those conjugated segments involved in charge transport at the buried semiconductor-dielectric interface of a field-effect device.
ACS Nano 2014 Jun 24
PMID:Mapping orientational order of charge-probed domains in a semiconducting polymer. 2481 31

Host-defense peptides (HDPs) are promising compounds against multidrug-resistant microbes. In vitro, their bactericidal and toxic concentrations are significantly different, but this might be due to the use of separate assays, with different cell densities. For experiments with a single cell type, the cell-density dependence of the active concentration of the DNS-PMAP23 HDP could be predicted based on the water/cell-membrane partition equilibrium and exhibited a lower bound at low cell counts. On the basis of these data, in the simultaneous presence of both bacteria and an excess of human cells, one would expect no significant toxicity, but also inhibition of the bactericidal activity due to peptide sequestration by host cells. However, this inhibition did not take place in assays with mixed cell populations, showing that for the HDP esculentin-1a(1-21)NH2, a range of bactericidal, nontoxic concentrations exists and confirming the effective selectivity of HDPs. Mixed-cell assays might be necessary to effectively asses HDP selectivity.
ACS Chem Biol 2017 01 20
PMID:Cell-Density Dependence of Host-Defense Peptide Activity and Selectivity in the Presence of Host Cells. 2793 73

Designing and synthesizing the ordered light-harvesting systems, possessing complementary absorption and energy-transfer process between the chromophores, are essential steps to accomplish successful mimicking of the natural photosynthetic systems. Metal-organic frameworks (MOFs) can be considered as an ideal system to achieve this due to their highly ordered structure, superior synthetic versatility, and tailorable functionality. Herein, we have synthesized the new light-harvesting mixed-ligand MOFs (MLMs, MLM-1-3) via solvothermal reactions between a Zr6 cluster and a mixture of appropriate ratio of 1,3,6,8-tetrakis(p-benzoic acid)pyrene and [5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrinato]-Zn(II) ligands. The identical symmetry and connectivity of the two ligands of the MLMs was the key parameter of successful synthesis as a single MOF form, and the ample overlap between the emission spectrum of pyrene and the absorption spectrum of porphyrin provided the ideal platform to design an efficient-energy transfer (EnT) process within the MLMs. We obtained the nanoscale maps of the fluorescence intensities and lifetimes of microsize MLM grains for unambiguous visualization of EnT phenomena occurring between two ligands in MLMs. Moreover, due to complementary absorption and energy transfer between the two ligands in the MLMs, our MLMs performed as superior photoinduced singlet-oxygen generators, verifying the enhanced light-harvesting properties of the pyrene- and porphyrin-based MLMs.
ACS Appl Mater Interfaces 2017 Nov 08
PMID:Efficient Energy Transfer (EnT) in Pyrene- and Porphyrin-Based Mixed-Ligand Metal-Organic Frameworks. 2904 58

Topical administration of anticancer drugs provides a potential chemotherapeutic modality with high patient compliance for cutaneous melanoma. However, the drug delivery efficiency is highly limited by physiological barriers from the skin to the tumor, which cannot acquire desired therapeutic efficacy. Herein, we propose a paintable oligopeptide hydrogel containing paclitaxel (PTX)-encapsulated cell-penetrating-peptide (CPP)-modified transfersomes (PTX-CTs) to enhance transdermal PTX delivery for topical melanoma treatment. After being plastered on the skin above the melanoma tumor, the PTX-CTs-embedded hydrogel (PTX-CTs/Gel) as a patch provided prolonged retention capacity of the PTX-CTs on the skin. The PTX-CTs with superior deformability could efficiently squeeze through the channels in the stratum coreum, and the surfactant components improved the fluidity of the lipid molecules in the stratum corneum to further enhance the skin permeation. Moreover, the CPP modification rendered the PTX-CT-enhanced penetration in the skin and tumor stroma as well as efficient transportation in the tumor cells. The PTX-CTs were shown to effectively slow the tumor growth in combination with the systemic chemotherapy using Taxol, the commercial PTX formulation on the xenograft B10F16 melanoma mouse model.
ACS Nano 2018 10 23
PMID:Enhanced Transdermal Drug Delivery by Transfersome-Embedded Oligopeptide Hydrogel for Topical Chemotherapy of Melanoma. 3018 53

We present a strategy for the fabrication of biomimetic nanoarrays, based on the use of DNA origami, that permits the multivalent investigation of ligand-receptor molecule interactions in cancer cell spreading, with nanoscale spatial resolution and single-molecule control. We employed DNA origami to control the nanoscale spatial organization of integrin- and epidermal growth factor (EGF)-binding ligands that modulate epidermal cancer cell behavior. By organizing these multivalent DNA nanostructures in nanoarray configurations on nanopatterned surfaces, we demonstrated the cooperative behavior of integrin and EGF ligands in the spreading of human cutaneous melanoma cells: this cooperation was shown to depend on both the number and ratio of the selective ligands employed. Notably, the multivalent biochips we have developed allowed for this cooperative effect to be demonstrated with single-molecule control and nanoscale spatial resolution. By and large, the platform presented here is of general applicability for the study, with molecular control, of different multivalent interactions governing biological processes from the function of cell-surface receptors to protein-ligand binding and pathogen inhibition.
ACS Nano 2019 01 22
PMID:DNA Origami Nanoarrays for Multivalent Investigations of Cancer Cell Spreading with Nanoscale Spatial Resolution and Single-Molecule Control. 3058 6