ACS Applied Bio Materials最新文献

A dual pH- and redox-responsive macromolecular prodrug of tacrolimus (TAC; FK506) was strategically developed through a stepwise approach involving the conjugation of hyaluronic acid (HA) with cystamine, followed by hydrazide functionalization and final coupling with succinate-modified tacrolimus. The resulting conjugate HA-cystamine-hydrazide-tacrolimus (HA-ss-NHNH₂-TAC or HSNT), confirmed by ¹H NMR, spontaneously formed stable micellar nanostructures as observed under a transmission electron microscope (TEM). The developed micelles possess an average particle size of about 200 nm, as measured by dynamic light scattering (DLS) and exhibited an acceptable polydispersity index, suggesting a relatively uniform and consistent size distribution. The developed system exhibited a high drug loading capacity (10.24%). Cellular uptake studies demonstrated that pretreatment of HCT-116 cells with excess HA to block CD44 receptors significantly reduced intracellular fluorescence, confirming receptor-mediated endocytosis of TAC/HSNT micelles. Further, hemolysis analysis showed less than 5% hemolysis upon incubation with red blood cells, highlighting the nonhemolytic and biocompatible nature of the micelles at the tested concentrations. The dual responsive polymeric micelles have the potential for further translational studies.

The silver nanoparticles were synthesized utilizing the Cordia macleodii (Griff.) Hook.F. & Thamos plant extract. The synthesis of nanoparticles was confirmed through UV-visible spectroscopy, exhibiting a distinct surface plasmon resonance (SPR) absorbance peak at 425 nm. Fourier-transform infrared spectroscopy (FTIR) analysis results revealed the different characteristic peaks corresponding to functional groups responsible for the reduction and stabilization of the silver nanoparticles. The X-ray diffraction (XRD) analysis confirmed a crystalline cubic structure with an average crystalline size of 13.31 nm. Dynamic light scattering (DLS) analysis revealed a hydrodynamic diameter of 114.50 nm with a polydispersity index (PDI) of 22% and a ζ-potential of -10.7 ± 0.8 mV. Field emission electron microscopy (FE-SEM) analysis of nanoparticles displayed a distinct spherical and oval-like shape with uniform morphology, and Engergy dispersive X-ray (EDX) mapping analysis confirmed the presence of Ag (93.39%), C (2.56%), and O (4.05%) by weight percentage. The High-resolution transmission electron microscopy (HR-TEM) exposed the silver nanoparticles as nearly spherical, with some aggregation, and an average diameter of 24.30 ± 11.13 nm. Inhibition in the growth of phytopathogenic bacteria Erwinia carotovora and Ralstonia solanacearum occurred at a 1000 μg/mL concentration of nanoparticles. Nanoparticles were found to accelerate the formation of reactive oxygen species (ROS). The antifungal activity of silver nanoparticles was observed at different concentrations of the nanoparticles. At a 1500 μg/mL concentration of nanoparticles, inhibition of growth was observed: 53.72% for Alternaria alternata, 59.00% for Aspergillus flavus, 53.23% for Botrytis cinerea, and 56.11% for Fusarium oxysporum. The antioxidant activity of silver nanoparticles showed 18.46% free radical scavenging through DPPH assay and 51.99% through ABTS assay at an 80 μg/mL concentration. This study provides an easy, eco-friendly method to fabricate silver nanoparticles for agricultural and other various applications.

Due to its noninvasiveness and high spatiotemporal selectivity, photodynamic therapy has been used clinically to treat superficial tumors for decades. However, the low tissue penetration of external excitation light makes it ineffective against deep-seated tumors and metastases. To fundamentally address this limitation, laser-free self-illuminating photodynamic therapy using internal light sources has emerged as a potential solution. It involves the use of platforms that are driven either through oxidative chemical excitation, such as chemiluminescence and bioluminescence, or radiological excitation from β-emitting isotopes in the form of Cherenkov luminescence. The electronic excitations generated are then transferred to the photosensitizers by different energy transfer mechanisms. This review offers a thorough overview of recent progress in self-illuminating PDT technologies, focusing on key energy transfer mechanisms such as resonance energy transfer, chemically induced electron exchange luminescence, and Cherenkov radiation energy transfer. We have used contemporary examples from the literature and critically analyzed the aspects that make these platforms successful as compared to conventional systems. In the end, we have presented a brief discussion on the current challenges with remedial measures and future perspectives of self-illuminating photodynamic therapy, which will help researchers to design new innovative internal light sources to overcome the major limitation of photodynamic therapy and further expand its application to deep-seated and metastatic tumors.

Management of wounds unveils various crucial clinical constraints, emphasizing the demand for transformed wound dressings that maximize the healing process and facilitate tissue regeneration. Here, a simple, green yet scalable approach was established to fabricate a multifunctional nanocomposite hydrogel employing plant- and animal-derived polymers, specifically almond gum and gelatin, enhanced with bioactive L-menthol and Ae-ZnONPs (MeZ@ALGEL), to improve wound healing by reinforcing the wound environment with its bactericidal, reactive oxygen species (ROS) regulation, and tissue regeneration abilities. MeZ@ALGEL exhibits necessary physicochemical and mechanical properties and significant antibacterial and antioxidant activities, making it ideal for topical administration and beneficial in accelerating wound repair. Under in vitro conditions, MeZ@ALGEL demonstrates a high degree of biocompatibility with fibroblast cells, actively promotes their migration in wound-like cases, and indicates improved hydroxyproline content with upregulation of Col-1, Col-3, Vegf genes, and downregulation of the Il-1b gene revealed in gene expression analysis. In vivo studies using Caenorhabditis elegans as a preliminary wound model reveal that the MeZ@ALGEL hydrogel is nontoxic up to the concentration of 125 μg/mL, promotes healing of glass wool-mediated wounds, exhibits strong antimicrobial activity, and accelerates wound repair through a multifaceted approach involving bacterial eradication, regulation of ROS, and stimulation of collagen synthesis, ultimately enhancing wound healing in the model organism. By these findings, the facilely synthesized nanocomposite hydrogel opens up the possibilities for developing multifunctional hydrogels of natural origin by utilizing the synergistic interaction of components and offers great potential in the wound care sector.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer with the poorest prognosis and lowest survival rate. Therefore, innovative therapeutic strategies, such as nucleic acid medicines, are required. However, vascular-mediated nucleic acid delivery remains a major challenge. In particular, when targeting tumors, it is more difficult to reach deep target cells because of the complex structures within the tumor microenvironment. A combination of physical energy and stimuli-responsive carriers is expected to easily break through barriers in this microenvironment. We have developed ultrasound-responsive nanobubbles (NBs) with lipid shells that serve as gene and nucleic acid delivery tools and ultrasound contrast agents. Furthermore, we reported that NBs containing anionic lipids have high in vivo stability and are useful as carriers of cationic molecules. In this study, we developed a simple and versatile method for loading nucleic acids onto the surfaces of anionic NBs, which are stable in vivo, by coating them with the cationic polysaccharide, methyl glycol chitosan (MGC). Additionally, the utility of the MGC-coated NBs (MGC-NBs) as systemic nucleic acid delivery tools was verified. Furthermore, we attempted to deliver microRNA-145, which serves as a tumor suppressor, to tumor-bearing mouse models of TNBC and evaluated the usefulness of our method for tumor therapy.

Breast reconstruction following oncoplastic breast-conserving surgery (OBCS) presents significant challenges, particularly in cases where conventional volume displacement techniques are insufficient. While autologous flaps offer an alternative, they are associated with donor site morbidity and surgical complexity. Acellular dermal matrix (ADM) has emerged as a promising volume replacement option, but its application in direct defect filling remains largely unexplored. This study introduced SC Fill paste, an injectable, microparticulate ADM developed through supercritical carbon dioxide (CO₂) decellularization, micronization, and dispersion, ensuring easy application and adaptability to irregular defect geometries. In vitro and in vivo assessments demonstrated efficient host tissue integration, preservation of the extracellular matrix (ECM) and essential growth factors, and minimal inflammatory response due to low double-stranded DNA (dsDNA) content and the absence of major histocompatibility complex (MHC-I) proteins, as confirmed by Western blot analysis. Additionally, SC Fill paste exhibited enhanced fibroblast infiltration and neovascularization and reduced capsular contracture compared to commercial controls. Matrix metalloproteinase (MMP) activity and collagen expression indicated a consistent six-month remodeling effect, ensuring long-term stability. These findings provide strong preclinical evidence supporting SC Fill paste as a versatile and effective reconstructive filler, offering a practical and adaptable solution for post-BCS defects.

Herein, we harnessed the transformative power of waste sugarcane-derived in situ nitrogen-doped carbon dots (N-CDs) to develop a fluorescent probe, poised to revolutionize the sensitive and selective detection of Bilirubin (BIL) in human urine. By utilizing waste sugarcane bagasse as the source of carbon and nitrogen, we embraced a combination of greener, solvent-free, and chemical-free thermal carbonization and the Sonochemical process to create N-CDs. The electronic, crystallographic, photochemical, and morphological behaviors of the synthesized N-CDs have been meticulously analyzed using various spectroscopic and microscopic techniques. When excited at 360 nm, these N-CDs emit a captivating blue fluorescence at 440 nm with an impressive color purity of 75.1%. Remarkably, the addition of BIL, without the need for labels on the N-CDs, results in a striking selective enhancement of this fluorescence with a striking color purity of 81%. This enhancement is driven by the formation of a ground-state interaction between BIL and the N-CDs, which is confirmed through a particle size analyzer and atomic force microscopy. The turn-on mechanism, which could be due to the formation of pi-pi stacking, is validated through FT-IR, and ¹H-NMR reveals the powerful interactions at play. This exceptional probe exemplifies unparalleled sensitivity, ultrastability, rapid response times, and unmatched accuracy for BIL concentrations ranging from 6.6 to 1876 nM, culminating in a limit of detection (LOD) of 3 nM, showcasing its efficacy in both synthetic urine samples and real human urine sample analysis with impressive recovery results. This study ignites inspiring insights into trailblazing approaches for quantifying BIL levels in urine, paving the way for significant advancements in noninvasive, stable, and accessible alternative medical diagnostics.

Estrogen receptor-positive (ER+) breast cancer is the predominant subtype of breast cancer, having significant therapeutic drawbacks, largely driven by undesired toxicity and drug resistance associated with conventional treatment regimens. Conjugating organoselenium moieties to various drugs or enzyme inhibitors can be a promising approach for the treatment of breast cancer with multimodal benefits in overcoming the limitations of conventional therapies. Herein, we report the synthesis and evaluation of a series of organoselenium–NBDHEX hybrids as potent anticancer agents. Based on the selective antiproliferative activities of these derivatives against ER+ breast cancer cells (MCF-7) over the nonmalignant cells (L132), the hybrid NHSe-2, having a 2-selenocyanatoacetyl linker, was chosen as the lead analogue for further studies. The compound NHSe-2 exhibited notable antiproliferative activity with S-phase arrest of cells and late-phase apoptosis in MCF-7 cells. Most importantly, NHSe-2 induced ROS-mediated degradation of HDAC4, NF-κB, and c-Myc, resulting in potent antiproliferation and eventually leading to apoptosis of MCF-7 cells. Moreover, it suppressed β-catenin expression, unlike NBDHEX; however, it retained GSTP1 inhibitory potency, indicating its add-on therapeutic potential. Therefore, NHSe-2 could be a potential anticancer agent and can be considered for further analysis for its multimodal activity in the realm of cancer research in the future.

Proper wound dressing is essential for ensuring and promoting effective wound healing. This study aimed to develop a novel porous composite wound dressing composed of aloe polysaccharide and collagen. The physical properties of aloe polysaccharide-collagen wound dressing (AP-CD) formulated in this study was characterized by scanning electron microscopy, energy dispersive spectroscopy, water absorption and air permeability tests. The safety and cytocompatibility of AP-CD were evaluated using CCK-8 and lactate dehydrogenase leakage rate assays. Besides, the effectiveness of AP-CD was assessed by measuring the wound healing rate. In vivo studies confirmed that AP-CD improved the wound healing rate and accelerated the healing process. Furthermore, AP-CD suppressed inflammatory response, promoted angiogenesis, increased the levels of growth factors and anti-inflammatory factors, and decreased the levels of pro-inflammatory factors. Single-cell sequencing analysis revealed a significant increase in the proportion of macrophages and T lymphocytes in AP-CD-treated wound tissue, accompanied by a notable decrease in fibroblast proportions. In summary, AP-CD demonstrated superior physical and chemical properties, good biocompatibility, and safety, making it a viable option for wound dressing. In vivo studies indicated that AP-CD effectively inhibited inflammatory responses and enhanced angiogenesis, thereby accelerating wound healing.

Due to the lack of relevant detection methods, the existence and function of the intestinal and placental alkaline phosphatase (IAP-PLAP) heterodimer remain largely elusive. Previously, we screened and obtained an aptamer, BG2, which exhibits specific recognition toward the IAP-PLAP heterodimer. Using BG2 as a probe, the heterodimer was found to be highly expressed on the membrane of various tumor cells as well as circulating tumor cells derived from clinical colorectal cancer samples, thus being regarded as a potential tumor marker. However, whether it is shed into extracellular fluid remains unclear. Herein, we developed a BG2-based chemiluminescence assay method with high sensitivity and selectivity for the detection of the IAP-PLAP heterodimer in biological fluids. Furthermore, based on the Na⁺-dependent binding between BG2 and the IAP-PLAP heterodimer, the captured proteins were successfully released and confirmed indeed IAP-PLAP heterodimer, indicating that they can be shed from the cell membrane into the culture medium. It was also found that the concentration of the IAP-PLAP heterodimer in the cell culture medium is closely correlated with its expression level on the cell membrane. Additionally, the levels of the heterodimer both on the cell membrane and in the culture medium were reduced in senescent cells. These results suggest that the IAP-PLAP heterodimer in body fluids may also serve as a disease marker. We further verified that this method can detect the IAP-PLAP heterodimer spiked in plasma samples with good recoveries, thus providing a method for liquid biopsy.