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Conventional enhanced permeation and retention (EPR) mediates the effects of many drugs, including the accumulation of nanocarriers at tumor sites, but its efficiency remains low. In this study, this limitation was overcome by developing a dual-targeting delivery system based on hyaluronan (HA, a major ligand of CD44) and tetraiodothyroacetic acid (tetrac, a specific ligand of α v β 3 ), which was exploited to carry docetaxel (DTX) for the synergistic active targeting to tumors. First, a tetrac-HA (TeHA) conjugate was synthesized and grafted onto the surfaces of solid lipid nanoparticles (SLNs) (TeHA-SLNs/DTX), with a high encapsulation efficiency of > 91.6%. The resulting SLNs exhibited an approximately toroid morphology revealed using TEM. The cellular uptake and cytotoxicity of various formulations on CD44/α v β 3 -enriched B16F10 cells were then assessed, and both results confirmed the selective uptake and high cytotoxicity of the TeHA-SLNs/DTX in a TeHA-dependent manner. In vivo imaging and vessel distribution tests revealed the efficiency of synergistic active targeting was higher than that of EPR-mediated passive targeting by the TeHA-SLNs to α v β 3 -expressing tumor blood vessels and CD44-expressing tumor cells via selective targeting. Finally, in both xenograft tumor mice and in situ lung metastasis tumor mice, tumor growth was significantly inhibited by TeHA-SLNs/DTX. Therefore, TeHA-SLNs are an efficient system for the dual-targeted delivery of drugs to treat cancer in vivo . [ABSTRACT FROM AUTHOR]

A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44 + melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro , the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo , miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse. [ABSTRACT FROM AUTHOR]

Phytochemical study of Valeriana jatamansi Jones afforded 45 compounds, including twenty-three iridoids (1 – 23), five sesquiterpenes (24 – 28), three steroids (29 – 31) and fourteen lignins (32 – 45). The structures of these compounds were assigned by detailed interpretation of spectroscopic data (1D and 2D NMR, HRESIMS) and comparisons with the published data. This is the first report of isolation of compounds (1 – 6 , 10 , 21 , 25 , 41 , 43 , 44 , 45) from Valerianaceae , compounds (13 , 27 , 39) within the genus Valeriana and compound 30 from V. jatamans. The chemotaxonomic data can support the genus Valeriana being accepted as a member of transitional taxa between the family Valerianaceae and Caprifoliaceae. Image 1 • This is the first report of isolation of compounds (1–6, 10, 21, 25, 41, 43, 44, 45) from Valerianaceae , compounds (13, 27, 39) within the genus Valeriana and compound 30 from V. jatamans. • The chemotaxonomic data can support the genus Valeriana being accepted as a member of transitional taxa between the family Valerianaceae and Caprifoliaceae. All the isolates were evaluated for cytotoxicity effect. [ABSTRACT FROM AUTHOR]

Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 week to > 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering. [ABSTRACT FROM AUTHOR]

Surgical removal remains the predominant treatment strategy for triple-negative breast cancer (TNBC). However, risks that include high locoregional recurrence and remote metastasis threaten patient survival and quality of life after surgery. In this study, a hydrogel based on poly (ethylene glycol) dimethacrylate and sericin methacryloyl was fabricated by photopolymerization to fill the resection cavity and prevent recurrence. The obtained hydrogel exhibited mechanical properties compatible with breast tissue and facilitated postsurgical wound management by promoting tissue regeneration. The DNA methylation inhibitor decitabine (DEC) and poly (lactic- co -glycolic acid)-encapsulated phytochemical gambogic acid (GA) were loaded into the hydrogel. The as-prepared hydrogel promoted fast release of DEC and sustained release of GA, leading to gasdermin E -mediated tumor cell pyroptosis and activating antitumor immune responses. Inducing postsurgical tumor cell pyroptosis inhibited local tumor recurrence and lung metastasis. While the dual-drug-loaded hydrogel system cured less than half of tumor-bearing mice, the cured mice survived for over half a year. These findings indicate that our hydrogel system is an excellent biocompatible platform for postsurgical TNBC therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Nanocarriers entering the body are usually coated by plasma protein, leading to a protein "corona" easily recognized by tissues and cells. Adjusting the composition of protein coronas may be an efficient way to change the properties and behavior of nanoparticles in vivo. In this study, we modified doxorubicin-loaded liposomes (Lip/DOX) with an albumin-binding domain (ABD) to prepare nanoparticles (ABD-Lip/DOX) that can specifically bind to albumin and form albumin-based protein coronas in vivo for targeted tumor therapy. The prepared liposomes were spherical with a particle size of about 100 nm. After incubating the liposomes with rat serum, the albumin content was eight times higher on ABD-Lip than on control liposomes. ABD-Lip significantly inhibited adsorption of IgG and complement activation in rat serum in vitro , while corona-coated ABD-Lip was internalized to a significantly greater extent than corona-coated control liposomes. In addition, ABD-Lip showed longer blood circulation time, higher tumor accumulation and greater antitumor efficacy than control liposomes in mice bearing 4 T1 tumors, while both liposome formulations showed similar biocompatibility. These results confirm that adjusting the component of protein coronas around nanoparticles can improve their therapeutic efficacy. [Display omitted] [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) drive malignant tumor progression, recurrence, and metastasis with unique characteristics, including self-renewal and resistance to conventional treatments. Conventional differentiation inducers, although promising, have limited cytotoxicity and may inadvertently enhance CSC stemness. To address these challenges, ongoing efforts are dedicated to developing strategies that can effectively combine both cytotoxicity and differentiation-inducing effects. In this study, we introduce oridonin (Ori), a small molecule with dual differentiation-inducing and cytotoxicity properties capable of eliminating tumor CSCs. We isolated CSCs in B16F10 cells using the Hoechst side population method and assessed the differentiation effect of Ori. Ori's differentiation-inducing effect was further evaluated using human acute promyelocytic leukemia. The cytotoxic potential of Ori against MCF-7 and B16F10 cell lines was assessed through various methods. In vivo anti-tumor and anti-CSC efficacy of Ori was investigated using mouse melanoma and CSCs melanoma models. Safety evaluation included zebrafish embryotoxicity and mouse acute toxicity experiments. As a result, Ori effectively dismantles tumorspheres, inhibits proliferation, and reduces the expression of CSC-specific markers. It induces significant differentiation, especially in the case of NB4. Additionally, Ori upregulates TP53 expression, mitigates the hypoxic tumor microenvironment, suppresses stemness, and inhibits PD-L1 expression, prompting a robust anti-cancer immune response. Ori demonstrates pronounced cytotoxicity, inducing notable pro-apoptotic effects on B16F10 and MCF-7 cells, with specific triggering of mitochondrial apoptosis. Importantly, Ori maintains a commendable biosafety record. The dual-action prowess of Ori not only induces the differentiation of CSCs but also dispatches differentiated and residual tumor cells, effectively thwarting the relentless march of tumor progression. Graphic summary illustrates the functions of Oridonin in cancer stem cells and cancer cells. Ori's dual role is to differentiate cancer stem cells and eliminate differentiated cancer cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] The entrapment efficiency of peptide loaded nanostructured lipid carriers (NLCs) could reach to 95%. [•] The porous nanoparticle-aggregate particles (PNAPs) powders could remain in lungs for a longer time than octreotide acetate (OA) solution and reach a sustained release. [•] The bioavailability was markedly enhanced by pulmonary deliver PNAPs compared with pulmonary deliver OA solutions and subcutaneous inject OA solution. [•] As far as we know, this is the first report on the anti-hepatic ischemia–reperfusion injury (HIRI) effects through intrapulmonary administration. [Copyright &y& Elsevier]

Methicillin-resistant Staphylococcus aureus (MRSA) is emerging as a serious pathogenic bacterium in the clinical setting, and antibiotic resistance is spreading faster than the introduction of new agents to kill such bacteria. In our study, Fusarium sp. 152, a marine fungus obtained from the South China Sea, was fermented to screen new anti-MRSA compounds including equisetin (EQ) with a MIC value of 1 µg/mL. Then, EQ was loaded into nanoparticle-based polyvinylpyrrolidone (PVP) electrospinning to facilitate its practical use. After electrospinning, the EQ nanofibers (EQ/NPs nanofiber) were 374.9 nm in diameter, and they showed a good flexibility and foldability. Additionally, the EQ/NPs nanofibers showed a better antibacterial effect both in vitro and in vivo than cefoxitin. Simultaneously, the infectious wounds treated with EQ/NPs nanofiber healed better and faster than those treated with EQ and cefoxitin. These findings strongly demonstrate that PVP-based electrospinning dressings are a candidate delivery carrier for the new anti-MRSA compound EQ for topical therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cur@PLGA-NPs are a novel AIE formulation capable of providing rich optical properties. • Hydrophobic interaction, electrostatic interaction, and π-π conjugation are responsible for the AIE properties. • The curcumin-based nano-AIE formulation could be successful used to image live cells. To revise the emission of curcumin (Cur) from "off" to "on", poly (D, L-lactide-co-glycolide) acid (PLGA) nanoparticles loaded with Cur were embedded in a polyvinyl alcohol (PVA) emulsifier (named Cur@PLGA-NPs). First, the emission intensities of different nanoformulations, including liposomes, bovine serum albumin (BSA) nanoparticles, and PLGA nanoparticles, were examined to discover the most effective carriers for Cur luminescence. As a result, Cur@PLGA-NPs exhibited the highest fluorescence intensity due to aggregation-induced emission (AIE), with quantum yields of 23.78% in aqueous solution and 21.52% in the solid state. According to X-ray diffraction (XRD) data, Cur@PLGA-NPs existed in the amorphous state, with a size of 217.2 ± 5.2 nm, an encapsulation efficiency (EE) of 69.98%, and a drug loading efficiency (LE) of 1.37%. The intramolecular interactions, which included hydrophobic interactions, electrostatic interactions, π-π interactions and solvatochromic effects, stabilized the chromophore cluster of Cur@PLGA-NPs in terms of nanoparticle formulation. Compared with free Cur, Cur@PLGA-NPs sensitized CT26 cells more efficiently with an IC 50 value of 16.9 μmol/L and an apoptotic rate of 17.20% at 10 μmol/L Cur. Because of the robust fluorescence emission based on AIE, Cur@PLGA-NPs were utilized as a nano-AIE probe for cell bioimaging, and many red fluorescent signals were observed in CT26 cells after treatment. These results suggest that Cur@PLGA-NPs provide a novel amorphous AIE formulation with imaging and bioactive capabilities. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sustained local anesthetics system can improve the satisfaction of patient. • Poloxamer 407 can release drugs sustained but with higher initial burst release. • Ropivacaine loaded injectable liposome-in-gel had low initial burst release. • Ropivacaine loaded gel was useful for local anesthesia without systemic toxicity. Reducing post-surgical pain can promote recovery of mobility, improve patient satisfaction, and reduce the risk of chronic pain syndrome. When managing post-surgical pain, single-injection local anesthesia is more convenient and involves lower risk to the patient than multi-injection regimes, but the effects are not long-lasting. Here we developed a system that can prolong local anesthesia after a single injection. In this system, ropivacaine (Ro) is encapsulated into liposomes, which are then loaded into Poloxamer 407-based thermosensitive hydrogels. The Ro-loaded liposome-in-gel system (Ro-Lip-Gel) is in a sol state before injection, and immediately after subcutaneous injection, it forms a gel in situ. We show through in vitro release and in vivo pharmacokinetics studies that this gel acts as a drug release depot. In rats, the initial burst release of Ro was smaller from Ro-Lip-Gel than from Ro solution or Ro-Gel, and Ro-Lip-Gel caused nerve blockade lasting four times longer than Ro solution. Ro-Lip-Gel degraded in vivo and showed good biocompatibility. Our results suggest that a liposome-in-gel system can show small initial burst release, long-term nerve blockade and good biocompatibility in vitro and in vivo. Therefore, such a system may be useful for sustained local anesthesia without systemic toxicity. [ABSTRACT FROM AUTHOR]