Phosphorus and Silicon-Based Macromolecules as Degradable Biomedical Polymers.

Synthetic polymers are indispensable in biomedical applications because they can be fabricated with consistent and reproducible properties, facile scalability, and customizable functionality to perform diverse tasks. However, currently available synthetic polymers have limitations, most notably when timely biodegradation is required. Despite there being, in principle, an entire periodic table to choose from, with the obvious exception of silicones, nearly all known synthetic polymers are combinations of carbon, nitrogen, and oxygen in the main chain. Expanding this to main-group heteroatoms can open the way to novel material properties. Herein the authors report on research to incorporate the chemically versatile and abundant silicon and phosphorus into polymers to induce cleavability into the polymer main chain. Less stable polymers, which degrade in a timely manner in mild biological environments, have considerable potential in biomedical applications. Herein the basic chemistry behind these materials is described and some recent studies into their medical applications are highlighted.

Supramolecular cancer photoimmunotherapy based on precise peptide self-assembly design.

Combinational photoimmunotherapy (PIT) is considered to be an ideal strategy for the treatment of highly recurrent and metastatic cancer, because it can ablate the primary tumor and provide in situ an autologous tumor vaccine to induce the host immune response, ultimately achieving the goal of controlling tumor growth and distal metastasis. Significant efforts have been devoted to enhancing the immune response caused by phototherapy-eliminated tumors. Recently, supramolecular PIT nanoagents based on precise peptide self-assembly design have been employed to improve the efficacy of photoimmunotherapy by utilizing the stability, targeting capability and flexibility of drugs, increasing tumor immunogenicity and realizing the synergistic amplification of immune effects through multiple pathways and collaborative strategy. This review summarizes peptide-based supramolecular PIT nanoagents for phototherapy-synergized cancer immunotherapy and its progress in enhancing the effect of photoimmunotherapy, especially focusing on the design of peptide-based PIT nanoagents, the progress of bioactive peptides combined photoimmunotherapy, and the synergistic immune-response mechanism.

Characterization and diabetic wound healing benefits of protein-polysaccharide complexes isolated from an animal ethno-medicine Periplaneta americana L.

Periplaneta americana L. (PA), a type of animal medicine, has been widely used for wound healing in clinical settings. In order to further investigate the bioactive wound healing substances in PA, crude PA protein-polysaccharide complexes were further purified by cellulose DE-52 and Sephadex G100 chromatography in succession. Among these isolated fractions, two fractions eluted by 0.3 M and 0.5 M NaCl with the higher yield, respectively named PaPPc2 and PaPPc3 respectively, were chosen for the wound healing experiments. Mediated by HPGPC, amino acid and monosaccharide composition analysis, circular dichroism spectrum, glycosylation type, FT-IR, and 1H NMR analysis, the characterization of PaPPc2 and PaPPc3 was implemented. And then, the benefits of PaPPcs to promote cell proliferation, migration, and tube formation of HUVECs were determined in vitro, indicated these fractions would facilitate angiogenesis. Finally, as proof of concept, PaPPc2 and PaPPc3 were employed to accelerate the acute wounds of diabetic mice, involving in increase blood vessels and the amounts of angiogenesis-related cytokines (α-SMA, VEGF, and CD31). In short, this study provides an experimental basis to demonstrate the protein-polysaccharide complexes of Periplaneta americana L. as its wound healing bioactive substances.

Pectic polysaccharides from Biluochun Tea: A comparative study in macromolecular characteristics, fine structures and radical scavenging activities in vitro.

In this study, two acidic Biluochun Tea polysaccharides (BTP-A11 and BTP-A12) were investigated comparatively, which mainly consisted of Rha, Ara, Gal and GalA, possibly suggesting their pectic nature. Structurally, their galacturonan backbones composed of →4)-α-D-GalpA-(1→ and →2)-α-L-Rhap-(1→ were revealed similar, while Ara- and Gal-based branches attached to the O-2 of →2)-α-L-Rhap-(1→ were in distinctive types, proportions, extensibilities and branching degrees. This could lead to their different macromolecular characteristics, where BTP-A11 with higher Mw presented a more hyper-branched chain conformation and relatively higher structural flexibility/compactness, thereby resulting in a lower exclusion effect and an insufficient hydrodynamic volume. Besides, better radical scavenging activities in vitro were also determined for Gal-enriched BTP-A11, where a larger surface area containing more H-donating groups were related to its higher Mw, more hyper-branched conformation, lower DM and higher DA. Therefore, the understanding of structure-property-activity relationships was improved to some degrees for acidic Biluochun Tea polysaccharides, which could be potentially required for more applications in food, medical and cosmetic fields.

Structural changes of lignin-carbohydrate complexes (LCCs) from Chinese quince fruits during the sequential fractionation of pectic and hemicellulosic polysaccharides.

Chinese quince (Chaenomeles sinensis) fruits offer a potential source of pectin and hemicellulose. However, the existence of lignin-carbohydrate complexes (LCCs) can negatively impact the extraction of pectin and hemicellulose. In this work, LCCs were sequentially fractionated from Chinese quince during the removal of pectin and hemicellulose. The structures of LCCs were characterized by HPAEC, FT-IR, GPC, Py-GC/MS, TGA and 2D HSQC NMR. The results showed that the carbohydrate content and molecular weight of LCCs was found to be changed significantly after the removal of hemicellulose (KSH). The lignin in Björkman LCCs was found to be linked mainly to galactan and fructan, whereas the lignin LCC-AcOHs was found to be linked mainly to arabinan after the removal of KSH. The isolation of carbonate-soluble pectin (NSP) increased thermal stability of Björkman LCC fraction, however, the isolation of chelator-soluble pectin (CSP) increased the thermal stability of LCC-AcOHs. The S/G ratios of LCC-AcOHs increased and large amounts of S-type lignin released during sequential fractionation of pectin and hemicellulose. These results will be beneficial for understanding the mechanisms of pectin and hemicellulose isolation, thereby facilitating the potential application of Chinese quince as a valuable natural resource for food and other industries.

Quantitative analysis of nine isoflavones in traditional Chinese medicines using mixed micellar liquid chromatography containing sodium dodecylsulfate/ß-cyclodextrin supramolecular amphiphiles.

Isoflavone is one of the phytoestrogens that have estrogenic effects, so it is usually served as an active ingredient for quality control of traditional Chinese medicines rich in isoflavones. Nine isoflavones commonly found in traditional Chinese medicines were separated in 30 min using mixed micellar liquid chromatography. The mobile phase consisted of 0.08 M sodium dodecylsulfate and 6.05 mM ß-cyclodextrin:methanol (87:13, v/v) at pH 3 and eluted isocratically at 1 mL/min through a C18 column. In this study, we systematically optimized the chromatographic conditions including the pH, the composition and concentration of surfactants, the type and ratio of organic solvents, and column temperature. The method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. There is no report using micellar liquid chromatography to detect isoflavones, and the optimized method has been successfully applied to quantify isoflavones in red clover and Radix Puerariae. This method is efficient, cheap, and convenient. Finally, we verified the existence of supramolecular amphiphilic vesicles in the mobile phase by transmission electron microscopy to explain the increased chromatographic efficiency.

Berberine-Based Heterogeneous Linear Supramolecules Neutralized the Acute Nephrotoxicity of Aristolochic Acid by the Self-Assembly Strategy.

Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, in vivo systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A-B) via electrostatic attraction and π-π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A-B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A-B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.

A supramolecular complex based on a Gd-containing polyoxometalate and food-borne peptide for MRI/CT imaging and NIR-triggered photothermal therapy.

A multifunctional supramolecular complex is reported for the integrated multiple magnetic resonance imaging/computed X-ray tomography (MRI/CT) imaging and photothermal therapy, wherein a gadolinium-substituted paramagnetic polyoxometalate cluster and food-borne antioxidant peptides identified from the trepang protein hydrolysates are introduced. The as-prepared complex maintained an uniform particle size and much better biocompatibility, and is an ideal candidate for the in vivo applications. The complex allows for T1-weighted MR imaging and a high Hounsfield unit value for enhanced CT imaging. Interestingly, we demonstrate that the complex possesses outstanding photothermal cancer-killing effects due to its high photothermal conversion efficiency under the exposure of an NIR laser and enhanced antibacterial activity to avoid bacterial infection from the thermal therapeutic process. These results indicate that the supramolecular complex platform exhibit potential for accurate medical diagnosis at an early stage and effective eradication of the tumor cells.

Fabrication and Characterisation of a Photo-Responsive, Injectable Nanosystem for Sustained Delivery of Macromolecules.

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.

Terminal Mono- and Bis-Conjugates of Oligonucleotides with Closo-Dodecaborate: Synthesis and Physico-Chemical Properties.

Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, the closo-dodecaborate anion represents a high-boron-containing residue with remarkable chemical stability and low toxicity, and is suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5'-, 3'-, or both terminal positions of DNA, RNA, 2'-O-Me RNA, and 2'-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3'-end of all oligomers stabilized their complementary complexes, whereas analogous 5'-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2'-O-methyl and 2'-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized the DNA/DNA duplex but gave a strong stabilization of the duplex with an RNA target. According to circular dichroism spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from the B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

Pillar[5]arene-Based Switched Supramolecular Photosensitizer for Self-Amplified and pH-Activated Photodynamic Therapy.

Photodynamic therapy (PDT) has emerged as a promising and spatiotemporally controllable cancer treatment modality. However, serious skin photosensitization during the PDT process limits the clinical application of PDT. Thus, the construction of "smart" and multifunctional photosensitizers has attracted substantial interest. Herein, we develop a mitochondria-targeting and pH-switched hybrid supramolecular photosensitizer by the host-guest interaction. The PDT efficacy of supramolecular photosensitizers can be quenched by the Förster resonance energy transfer (FRET) effect during long circulation and activated by the dissociation of supramolecular photosensitizers in an acidic tumor microenvironment, benefitting from the dynamic feature of the host-guest interaction and pH responsiveness of the water-soluble pillar[5]arene on gold nanoparticles. The rational integration of mitochondria-targeting and reductive glutathione (GSH) elimination in the hybrid switchable supramolecular photosensitizer prolongs the lifetime of reactive oxygen species generated in the PDT near mitochondria and further amplifies the PDT efficacy. Thus, the facile and versatile construction of switchable supramolecular photosensitizer offers not only the targeted and precise phototherapy but also high therapeutic efficacy, which would provide a new path for the clinic application of PDT.

Supramolecular insight into the substitution of sulfur by selenium, based on crystal structures, quantum-chemical calculations and biosystem recognition.

Statistical analysis of data from crystal structures extracted from the Cambridge Structural Database (CSD) has shown that S and Se atoms display a similar tendency towards specific types of interaction if they are part of a fragment that corresponds to the side chains of cysteine (Cys), methionine (Met) selenocysteine (Sec) and selenomethionine (Mse). The most numerous are structures with C-H...Se and C-H...S interactions (∼80%), notably less numerous are structures with Se...Se and S...S interactions (∼5%), and Se...π and S...π interactions are the least numerous. The results of quantum-chemical calculations have indicated that C-H...Se (∼-0.8 kcal mol-1) and C-H...S interactions are weaker than the most stable parallel interaction (∼-3.3 kcal mol-1) and electrostatic interactions of σ/π type (∼-2.6 kcal mol-1). Their significant presence can be explained by the abundance of CH groups compared with the numbers of Se and S atoms in the crystal structures, and also by the influence of substituents bonded to the Se or S atom that further reduce their possibilities for interacting with species from the environment. This can also offer an explanation as to why O-H...Se (∼-4.4 kcal mol-1) and N-H...Se interactions (∼-2.2 kcal mol-1) are less numerous. Docking studies revealed that S and Se rarely participate in interactions with the amino acid residues of target enzymes, mostly because those residues preferentially interact with the substituents bonded to Se and S. The differences between Se and S ligands in the number and positions of their binding sites are more pronounced if the substituents are polar and if there are more Se/S atoms in the ligand.

Subnanometer-resolution structure determination in situ by hybrid subtomogram averaging - single particle cryo-EM.

Cryo-electron tomography combined with subtomogram averaging (StA) has yielded high-resolution structures of macromolecules in their native context. However, high-resolution StA is not commonplace due to beam-induced sample drift, images with poor signal-to-noise ratios (SNR), challenges in CTF correction, and limited particle number. Here we address these issues by collecting tilt series with a higher electron dose at the zero-degree tilt. Particles of interest are then located within reconstructed tomograms, processed by conventional StA, and then re-extracted from the high-dose images in 2D. Single particle analysis tools are then applied to refine the 2D particle alignment and generate a reconstruction. Use of our hybrid StA (hStA) workflow improved the resolution for tobacco mosaic virus from 7.2 to 4.4 Å and for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. These resolution gains make hStA a promising approach for other StA projects aimed at achieving subnanometer resolution.

Supramolecular hydrogels based on cellulose for sustained release of therapeutic substances with antimicrobial and wound healing properties.

A multifaceted hydrogel-based formulation was reported. The hydrogel was prepared by crosslinking cellulose and substituted chalcone. Moreover, the formulation was conjugated with carbon nanotubes with the aim of increasing the loading amount of bioactive compounds such as allantoin, dexpanthenol, resveratrol and linezolid. The hydrogel formation was confirmed by swelling tests, FT-IR spectroscopy, thermogravimetric analysis and SEM. The hydrogel showed an improved release rate of therapeutic substances, exhibiting a simultaneous and coordinated release according to the chromatographic studies. The efficacy of drug release was confirmed by wound closure and in vivo wound healing studies that showed promising healing results. The antibacterial assays demonstrated that the sustained release of linezolid tends to be very effective. In conclusion, a multifaceted formulation based on carbon nanotube-containing cellulose-chalcone was developed that can potentially be utilized in treating complex wounds owing to its improved wound healing properties and prevention of potential infections.

Targeted anticancer prodrug therapy using dextran mediated enzyme-antibody conjugate and ß-cyclodextrin-curcumin inclusion complex.

A targeted and controlled drug delivery system based on ß-cyclodextrin (ß-CD) for encapsulation and controlled release of hydrophobic drugs in the presence of maltogenic amylase (MAase), as a cyclodextrin-hydrolyzing enzyme, and trastuzumab antibody has been developed. In this study, the inclusion complex of curcumin (CUR), as a model anticancer compound, with ß-CD was prepared and we constructed an antibody-enzyme bioconjugate (dextran mediated MAase-Trastuzumab bioconjugate) for controlled and targeted release of CUR at HER2 positive cancer cells (including SKBR3 and BT474). Immunocytochemistry analysis indicated that the MAase-Trastuzumab bioconjugate had significant binding affinities to HER2 positive cancer cells and demonstrated high enzyme activity to degrade ß-CD in order to rapid release of CUR on targeted cell surface. Fluorescence microscopy images and cytotoxicity studies represent significantly greater cellular uptake and anti-proliferative effects of CUR by ß-CD-CUR/MAase-Trastuzumab bioconjugate compared to free CUR and ß-CD-CUR in presence and absence of MAase in HER2 positive cells. The results from flow cytometric assay suggest that the ß-CD-CUR/MAase-Trastuzumab conjugate exhibited higher cytotoxic and apoptotic effects on cancer cells compared to other formulation. We demonstrate that this formulation has a potential application for targeted and controlled release of drugs in cancer therapy with increased therapeutic efficiency.

Main-Chain Phosphorus-Containing Polymers for Therapeutic Applications.

Polymers in which phosphorus is an integral part of the main chain, including polyphosphazenes and polyphosphoesters, have been widely investigated in recent years for their potential in a number of therapeutic applications. Phosphorus, as the central feature of these polymers, endears the chemical functionalization, and in some cases (bio)degradability, to facilitate their use in such therapeutic formulations. Recent advances in the synthetic polymer chemistry have allowed for controlled synthesis methods in order to prepare the complex macromolecular structures required, alongside the control and reproducibility desired for such medical applications. While the main polymer families described herein, polyphosphazenes and polyphosphoesters and their analogues, as well as phosphorus-based dendrimers, have hitherto predominantly been investigated in isolation from one another, this review aims to highlight and bring together some of this research. In doing so, the focus is placed on the essential, and often mutual, design features and structure-property relationships that allow the preparation of such functional materials. The first part of the review details the relevant features of phosphorus-containing polymers in respect to their use in therapeutic applications, while the second part highlights some recent and innovative applications, offering insights into the most state-of-the-art research on phosphorus-based polymers in a therapeutic context.

Biologically active macromolecules: Extraction strategies, therapeutic potential and biomedical perspective.

Marine biome exhibits an immense essence of excellence and enriched with high-value bioactive compounds of therapeutic and biomedical value. During the past several years, an array of biologically active molecules has been extracted/isolated and purified from numerous sources of marine origin with the aid of distinct techniques and methodologies for newer applications. The growing demand for bioactive molecules with unique functionalities in various industrial divisions, such as therapeutic sectors and biomedical, has endorsed the necessity for highly suitable and standardized strategies to extract these bioactive components using a state-of-the-art and inexpensive measures. This is also because many in practice conventional extraction methodologies suffer from processing limitations and low-yield issues. Besides that, other major issues include (i) decrease efficacy, (ii) excessive energy cost, (iii) low yield, (iv) lower cost-effective ratio, (v) minimal selectivity, (vi) low activity, and (vii) stability, etc. In this context, there is an urgent need for new and robust extraction strategies. The synergies of modern extraction techniques with efficient and novel pretreatment approaches, such as the integration of enzymes, accompanied by conventional extraction processes, should be the utmost goal of current research and development studies. The typical effectivity of the extraction techniques mostly relies on these points, i.e., (i) know-how about the source nature and type, (ii) understanding the structural and compositional profile, (iii) influence of the processing factors, (iv) interplay between the extraction conditions and the end-product, (v) understanding the available functional entities, (vi) reaction chemistry of the extract bioactive compounds, and (vii) effective exploitation of the end-product in the marketplace. Marine biome, among numerous naturally occurring sources, has been appeared an immense essence of excellence to isolate an array of biologically active constituents with medicinal values and related point-of-care applications. Herein, we reviewed the salient information covering various therapeutic potential and biomedical perspectives. Following a brief introduction and marine pharmacognosy, an array of high-value biomolecules of marine origin are discussed with suitable examples. From the robust extraction strategies viewpoint, a part of the review focuses on three techniques, i.e., (1) enzyme-assisted extraction (EAE), (2) supercritical-fluid extraction (SFE), and (3) microwave-assisted extraction (MAE). Each technique is further enriched with processing and workflow environment. The later part of the review is mainly focused on the therapeutic and biomedical perspectives of under-reviewed bio-active compounds or biomolecules. The previous and latest research on the anticancer, skin curative, cardio-protective, immunomodulatory and UV-protectant potentialities of marine-derived biologically active entities have been summarized with suitable examples and related pathways illustrations. Finally, the work is wrapped-up with current research challenges, future aspects, and concluding remarks.

Macromolecular Targets of Antiparasitic Germacranolide Sesquiterpenoids: An In Silico Investigation.

BACKGROUND: The parasitic protozoal infections leishmaniasis, human African trypanosomiasis, and Chagas disease are neglected tropical diseases that pose serious health risks for much of the world's population. Current treatment options suffer from limitations, but plantderived natural products may provide economically advantageous therapeutic alternatives. Several germacranolide sesquiterpenoids have shown promising antiparasitic activities, but the mechanisms of activity have not been clearly established. OBJECTIVE: The objective is to use in silico screening of known antiparasitic germacranolides against recognized protozoal protein targets in order to provide insight into the molecular mechanisms of activity of these natural products. METHODS: Conformational analyses of the germacranolides were carried out using density functional theory, followed by molecular docking. A total of 88 Leishmania protein structures, 86 T. brucei protein structures, and 50 T. cruzi protein structures were screened against 27 antiparasitic germacranolides. RESULTS: The in-silico screening has revealed which of the protein targets of Leishmania spp., Trypanosoma brucei, and Trypanosoma cruzi are preferred by the sesquiterpenoid ligands.

New structural insights into the recognition of undamaged splayed-arm DNA with a single pair of non-complementary nucleotides by human nucleotide excision repair protein XPA.

XPA (Xeroderma pigmentosum complementation group A) is a core scaffold protein that plays significant roles in DNA damage verification and recruiting downstream endonucleases in the nucleotide excision repair (NER) pathway. Here, we present the 2.81 Å resolution crystal structure of the DNA-binding domain (DBD) of human XPA in complex with an undamaged splayed-arm DNA substrate with a single pair of non-complementary nucleotides. The structure reveals that two XPA molecules bind to one splayed-arm DNA with a 10-bp duplex recognition motif in a non-sequence-specific manner. XPA molecules bind to both ends of the DNA duplex region with a characteristic ß-hairpin. A conserved tryptophan residue Trp175 packs against the last base pair of DNA duplex and stabilizes the conformation of the characteristic ß-hairpin. Upon DNA binding, the C-terminal last helix of XPA would shift towards the minor groove of the DNA substrate for better interaction. Notably, human XPA is able to bind to the undamaged DNA duplex without any kinks, and XPA-DNA binding does not bend the DNA substrate obviously. This study provides structural basis for the binding mechanism of XPA to the undamaged splayed-arm DNA with a single pair of non-complementary nucleotides.

A self-assembled supramolecular natural product gel from liquidambaric acid in traditional Chinese medicine with inherent anti-inflammatory activity for drug delivery.

Self-assembled supramolecular gels as a soft material have received extensive attention due to their excellent physicochemical properties such as variability, multiple responsiveness and appropriate viscoelasticity. At present, many self-assembled gels with physicochemical functions are constructed as drug delivery systems and used for the treatment of diseases. However, self-assembled gel drug delivery systems having pharmacological functions remain almost unexplored. Here, we present an anti-inflammatory pharmacologically active gel drug delivery system consisting of direct self-assembled small molecule naturally-occurring compounds (self-assembled small molecule natural products, SSNPs) derived from traditional Chinese medicine. The system not only exhibits excellent thixotropy, good topical safety and sustained release, but also achieves superior inflammatory therapeutic effects both in vivo and in vitro. Compared to non-pharmacologically active drug delivery systems, this system can increase the in vivo anti-inflammatory activity of drugs by nearly two-thirds. More importantly, its therapeutic effect even reached 141.54% of OTC drugs. The successful construction of an anti-inflammatory pharmacologically active gel drug delivery system not only makes full use of the self-assembly properties and biological activity of natural products, but also provides an important reference for the development of pharmacologically active drug delivery systems using SSNPs in the future.