Melanoma either intrinsically possesses resistance or rapidly acquires resistance to anti-tumor therapy, which often leads to local recurrence or distant metastasis after resection. In this study, we found histone 3 lysine 27 (H3K27) demethylated by an inhibitor of histone methyltransferase EZH2 could epigenetically reverse the resistance to chemo-drug paclitaxel (PTX), or enhance the efficacy of immune checkpoint inhibitor anti-TIGIT via downregulating TIGIT ligand CD155. Next, to address the complexity in the combination of multiple bioactive molecules with distinct therapeutic properties, we developed a polysaccharides-based organohydrogel (OHG) configured with a heterogenous network. Therein, hydroxypropyl chitosan (HPC)-stabilized emulsions for hydrophobic drug entrapment were crosslinked with oxidized dextran (Odex) to form a hydrophilic gel matrix to facilitate antibody accommodation, which demonstrated a tunable sustained release profile by optimizing emulsion/gel volume ratios. As results, local injection of OHG loaded with EZH2 inhibitor UNC1999, PTX and anti-TIGIT did not only synergistically enhance the cytotoxicity of PTX, but also reprogrammed the immune resistance via bi-directionally blocking TIGIT/CD155 axis, leading to the recruitment of cytotoxic effector cells into tumor and conferring a systemic immune memory to prevent lung metastasis. Hence, this polysaccharides-based OHG represents a potential in-situ epigenetic-, chemo- and immunotherapy platform to treat unresectable metastatic melanoma.

Dihydrazide (ADH) and dioxyamine (PDHA) were assessed for their efficacy in coupling chitosan and dextran via their reducing ends. Initially, the end-functionalization of the individual polysaccharide blocks was investigated. Under non-reducing conditions, chitosan with a 2,5-anhydro-D-mannose unit at its reducing end exhibited high reactivity with both PDHA and ADH. Dextran, with a normal reducing end, showed superior reactivity with PDHA compared to ADH, although complete conversion with ADH could be achieved under reductive conditions with NaBH3CN. Importantly, the oxime bond in PDHA conjugates exhibited greater stability against hydrolysis compared to the hydrazone bond in ADH conjugates. The optimal block coupling method consisted in reacting chitosan with an excess of dextran pre-functionalized with PDHA. The copolysaccharides could be synthesized in high yields under both reducing and non-reducing conditions. This methodology was applied to relatively long polysaccharide blocks with molecular weight up to 14,000 g/mol for chitosan and up to 40,000 g/mol for dextran. Surprisingly, block copolysaccharides did not self-assemble at neutral or basic pH; rather, they precipitated due to hydrogen bonding between neutralized amino groups of chitosan. However, nanoparticles could be obtained through a nanoprecipitation approach.

Magnetic nanoparticles used for targeted drug administration present a promising approach in cancer treatment owing to its notable advantages, such as targeted and enhanced encapsulation ability and improved bio protection compared with conventional drug delivery methods. Au shell-iron core nanoparticles (Fe3O4@Au) were manufactured by a chemical process, coated with dextran to encapsulate curcumin, and functionalized for precision drug delivery using folic acid to combat liver cancer. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, vibrational spectroscopy, and magnetometry were applied to assess the synthesis of the Fe3O4@Au-DEX-CU-FA compound. The mean size, zeta potential, and polydispersity of Fe3O4@Au-DEX-CU-FA were 63.3 ± 2.33 nm, -68.3 ± 1.78 mV, and 0.041 ± 0.008, respectively. Molecular docking models were created to examine the relationship between Fe3O4@Au-CU and BCL-XL, BAK, and to identify potential binding sites. The loading efficiency and release profile tests examined the medication delivery system\'s ability. MTT assay was subsequently utilized to determine the optimal dosage and therapeutic efficacy of Fe3O4@Au-DEX-CU-FA on cancer SNU-449 and healthy THLE-2 cell lines. Flow cytometry demonstrated that Fe3O4@Au-DEX-CU-FA effectively induced cancer cell death. Fe3O4@Au-DEX-FA showed a regulated release profile of free curcumin at 37 °C and pH values of 7.4 and 5.4. Real-time PCR revealed increased BAK expression and decreased BCL-XL expression. Nude tumor-bearing mice were used for in vivo experiments. Fe3O4@Au-DEX-CU-FA treatment dramatically reduced the swelling size compared with free CU and control treatments. It also resulted in a longer lifespan, expanded splenocyte proliferation, increased IFN-γ levels, and decreased IL-4 levels. The regular cells showed no cytotoxic effect compared with the cancer type, confirming that Fe3O4@Au-DEX-CU-FA maintained its potent anticancer actions. The data suggests that Fe3O4@Au-DEX-CU-FA possesses a promising potential as a therapeutic agent for combating tumors.

An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives.

Nuclear medicine is an important tool for use in molecular imaging of important biological processes. Methods for intravenous delivery of radiotracers remains a challenge, with tail vein injections demonstrated to be technically difficult and lacking in reproducibility. Other intravenous methods include jugular vein (JV) injection, which requires a more invasive and precise microsurgical technique. Although the retroorbital (RO) sinus drains directly into the JV, and RO injections are minimally invasive and simpler to perform, they remain underutilized, perhaps due to a lack of studies demonstrating their performance. This study provides a comprehensive comparison of dynamic tissue biodistribution of three categories of commonly utilized radiopharmaceuticals between JV and RO injection methods in prostate tumor-bearing mice using PET-CT imaging. Results show that JV and RO injections have equivalent dynamic tissue biodistributions across the three categories of radiopharmaceuticals used: (1) small molecule measuring tumor metabolism (18F-flurodeoxyglucose [FDG]); (2) peptide-based probe measuring angiogenesis (64Cu-NOTA-PEG4-cRGD2); and (3) dextran-based nanocarrier (64Cu-NOTA-D20). Although RO injections present with some limitations such as type of injectate and difficulty for measuring acute, dynamic pharmacokinetics, this study demonstrates that RO injections are a viable, minimally invasive or stressful, and efficient alternative intravenous delivery technique for molecular imaging.

Designing hydrogel dressing with intrinsic antibacterial property to promote skin injury recovery remains a significant challenge. In this research, poly(aspartic hydrazide) with grafted betaine (PAHB) was designed and reacted with oxidized dextran (OD) to fabricate biodegradable PAHB/OD hydrogel and its application as wound dressing was systematically investigated. The PAHB/OD hydrogels exhibited fast gelation, strong tissue adhesion, preferable mechanical properties and biocompatibility. The grafted betaine endowed the hydrogel with antibacterial property and antibacterial rate enhanced through photothermal performance of composited CuS nanoparticles under near infrared (NIR) radiation. The CuS composited PAHB/OD hydrogel (CuS/hydrogel) with microporous morphology was used as burn wound dressing with loaded anti-inflammatory drug diclofenac sodium (DS) in mouse model. The results showed the DS loaded CuS/hydrogel (CuS@DS/hydrogel) promoted the tissue regeneration and suppressed the inflammatory response. The histological analysis and immunohistochemical expression confirmed the CuS@DS/hydrogel promote angiogenesis of the burn wound by regulating the expression of inflammatory cytokines (IL-6 and CD68) and vascular endothelial growth factor (VEGF). Overall, the CuS@DS/hydrogel hydrogel is a promising candidate as wound dressing due to its tissue adhesive, antioxidant, antibacterial and anti-inflammatory activities.

A series of injectable polysaccharide hydrogels were prepared with oxidized dextran and diethylenetriamine-modified carboxymethylcellulose or hyaluronic acid. Rheological evaluation revealed that carboxymethylcellulose-based hydrogels achieved the largest storage moduli (>1 kPa) when prepared from 5 wt. % solutions. However, carboxymethylcellulose-based hydrogels with storage moduli >100 Pa were prepared from solutions with concentrations as low as 2 wt. %. Hyaluronic acid-based hydrogels demonstrated smaller storage moduli but had swelling ratios more than four times that of the carboxymethylcellulose systems at the same polymer concentrations. The incorporation of N-diazeniumdiolate NO donors into the hydrogels resulted in reduced hydrogel storage moduli as a function of NO donor concentration. The impact of the hydrogel architecture on NO-release kinetics proved dependent on the identity of the NO donor. Hydrogel degradation over 14 d was measured at pH 5.4 and 7.4 and indicated that hyaluronic acid-based hydrogels degraded more rapidly than carboxymethylcellulose hydrogels and that the addition of NO to the hydrogels increased the rate at which they degraded. In vitro cytotoxicity of hydrogel extracts was evaluated against five cell lines, with no observed toxicity except for that of hyaluronic acid-based hydrogel extracts against human gingival fibroblasts. The diverse properties, versatility, and non-toxic characteristics of these injectable hydrogels should facilitate local delivery of nitric oxide for a range of biomedical applications.

Dental caries is a worldwide public healthcare concern, and is closely related to the acidic environment that caused by bacterial decomposition of food. In this study, a two-step ion exchange liquid-phase stripping method was applied to strip out vermiculite (VMT) nanosheets, then amorphous calcium phosphate (ACP) and dextran were inserted between the VMT nanosheets interlayer to obtain a composite two-dimension nanosheets (VMT/ACP/Dextran). VMT/ACP/Dextran composite nanosheets exhibited excellent biocompatibility and could provide exogenous Ca2+and PO43- from ACP, provide SiO44-, Mg2+, Fe2+ and obtain buffering pH and antibacterial properties from VMT, as well as improve suspension stability and targeting Streptococcus mutans through glucan. The in vitro study showed that the composite materials could promote the mineralization and sealing of dentin tubules by releasing active ions, buffer pH 4.5 (a value close to the pH in the dental plaque environment) to pH 6.6-7.1 (values close to the pH in human saliva) through ion exchange, and exert antibacterial effects by targeting Streptococcus mutans and exerting oxidase like and peroxidase like activities to produce reactive oxygen species (ROS). The in vivo animal study showed that daily cleaning teeth using VMT/ACP/Dextran composite nanosheets could effectively reduce the incidence rate and severity of dental caries in rats. Taking together, the developed VMT/ACP/Dextran composite nanosheets, which integrated the excellent properties of VMT, ACP and dextran, can effectively prevent dental caries through a combination of factors such as buffering acids, antibacterial properties, and promoting calcification, and may be used as an active ingredient for daily oral hygiene or filling materials to prevent and treat dental caries.

The search for novel exopolysaccharides (EPS) with targeted functionalities is currently a topic of great interest. This study aimed to investigate the chemical characteristics and technological properties of a novel EPS (named EPS_O) from Leuconostoc mesenteroides. EPS_O was a high-molecular-weight dextran (>6.68 × 105 g/mol) characterized by high water-holding capacity (785 ± 73%) and high water solubility index (about 99%). EPS_O in water (<30 mg/mL) formed viscous solutions, whereas at concentrations >30 mg/mL, it formed weak gels. Notably, lower concentrations (4-5 mg/mL) exhibited antimicrobial activity against various foodborne pathogens, antibiofilm activity against Listeria monocytogenes, and radical-scavenging activity. These properties are significant for maintaining food quality and promoting health. Based on these findings, EPS_O presents itself as a promising food ingredient that could elevate food quality and confer health benefits to consumers.

Leuconostoc citreum JZ-002 was extracted from artisanal orange wine. This strain was used to synthesize dextran with a purification extraction of 27.9 g/L. The resulting dextran had a molecular weight of 2.45 × 106 Da. A significant portion, amounting to 64 % of the structure, is constituted by the main chain, with α-(1,6) glycosidic bonds acting as the linkages. In contrast, the branched chain, comprising 34 % of the entire molecule, is characterized by the presence of α-(1,3) glycosidic bonds. The dextransucrase DsrB, believed to be accountable for the formation of the dextran backbone, was successfully cloned into the pET-28a-AcmA vector. The recombinant expression of the enzyme was achieved. Purified recombinant enzymes and immobilized in a single go using the gram-positive enhancer matrix (GEM). The maximum yield of dextran produced by suchimmobilized enzyme was 191.9 g/L. The composition featured a dextran connected via α-(1,6) glycosidic linkages. Molecular weight controlled synthesis was achieved with sucrose concentrations of 100-2000 mM and enzyme concentrations of 320-1280 U. The Mw of the synthesized dextran extended from 4680 to 1,320,000 Da. By controlling the ratio between enzyme concentration and sucrose concentration, dextrans with diverse Mw can be enzymatically generated.