The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis
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ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC11017612 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.
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Project description:Nanoparticle-mediated targeted delivery of bioactive natural compounds has recently been gaining much interest for breast cancer therapy. Herein, phenyl boronic acid (PBA)-conjugated and pH-responsive ZnO nanoparticles (diameter ∼40 nm) were synthesized for the tumor tissue-specific delivery of curcumin. PBA conjugation facilitates the targeted delivery of curcumin to the sialic acid overexpressed in breast cancer cell membranes. Curcumin-loaded ZnO nanoparticles (ZnO-PBA-Curcumin) caused apoptotic cell death in MCF-7 human breast cancer cells by inducing oxidative stress and mitochondrial damage. Further, in vivo intravenous (i.v.) administration of ZnO-PBA-Curcumin was found to effectively decrease tumor growth in Ehrlich ascites carcinoma (EAC) tumor-bearing mice via the enhanced accumulation of curcumin. Interestingly, ZnO-PBA-Curcumin did not show any signs of systemic toxicity. The cytotoxic potential of the nanohybrid ZnO-PBA-Curcumin is attributed to the combinatorial cytotoxic effects of curcumin and ZnO in cancer cells. Collectively, ZnO-PBA-Curcumin may represent a potential treatment modality for breast cancer therapy. This study provides insight into the tumor cell targeting mechanism using PBA functionalization, and the anticancer efficacy of curcumin-loaded pH-sensitive nanohybrids can be attributed to the differential oxidative stress-inducing properties of curcumin and Zn+2 ions.
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Project description:Stable and monodisperse phenylboronic acid-functionalized nanoparticles (PBA-NPs) were fabricated using 3-((acrylamido)methyl)phenylboronic acid homopolymer (PBAH) via solvent displacement technique. The effect of operating parameters, including stirring time, initial polymer concentration and the proportion of methanol on the self-assembly process were systematically investigated. The diameters of the PBA-NPs were increased as increasing the initial PBAH concentration and the proportion of methanol. Likewise, there was a linear dependence between the size of self-assembled nanoparticles and the polymer concentration. Moreover, the dissipative particle dynamics (DPD) simulation technique was used to investigate the mechanism of self-assembly behavior of PBAH, which indicated that the interior of PBA-NPs was hydrophobic and compact, and the boronic acid groups were displayed on both the outermost and interior of PBA-NPs. The resulting PBA-NPs could successfully encapsulate emodin through PBA-diol interaction and the encapsulation efficiency (EE%) and drug loading content (DLC%) of drug-loaded PBA-NPs were 78% and 2.1%, respectively. Owing to the acid-labile feature of the boronate linkage, a reduction in environmental pH from pH 7.4 to 5.0 could trigger the disassociation of the boronate ester bonds, which could accelerate the drug release from PBA-Emodin-NPs. Besides, PBA-Emodin-NPs showed a much higher cytotoxicity to HepG2 cells (cancer cells) than that to MC-3T3-E1 cells (normal cells). These results imply that PBA-NPs would be a promising scaffold for the delivery of polyphenolic drugs.
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Project description:The development of nanomedicines provides new opportunities for the treatment of atherosclerosis (AS) due to their great advantages such as the improved drug solubility, enhanced bioavailability and reduced side effects. Despite these advantages, nanomedicines are still facing some challenges. The problems remain in the short circulation life, lack of specific targeting and poor drug release controllability. In order to overcome the shortages of conventional nanomedicines, the combination of biomimetic strategy with smart nanoagents has been proposed. In light with the high reactive oxygen species (ROS) level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS, we fabricated ROS-responsive biomimetic nanoparticles (NPs), which camouflaged macrophage membrane (MM) on ROS-responsive NPs loaded with rapamycin (RNPs) for potential application in AS therapy. The resulting ROS-responsive biomimetic NPs (MM/RNPs) exhibited favorable hydrodynamic size with negative surface charge, retained the functional proteins from MM, and showed ROS-responsive drug release. Because of the biomimetic camouflaging on surface, MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells. Meanwhile, MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro. Furthermore, the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation. Consequently, these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.
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Project description:Soil enzymes, such as invertase, urease, acidic phosphatase and catalase, play critical roles in soil biochemical reactions and are involved in soil fertility. However, it remains a great challenge to efficiently concentrate soil enzymes and sensitively assess enzyme activity. In this study, we synthesized phenylboronic acid-functionalized magnetic nanoparticles to rapidly capture soil enzymes for sensitive soil enzyme assays. The iron oxide magnetic nanoparticles (MNPs) were firstly prepared by the co-precipitation method and then functionalized by (3-aminopropyl)triethoxysilane, polyethyleneimine and phenylboric acid in turn, obtaining the final nanoparticles (MNPPBA). Protein-capturing assays showed that the functionalized MNPs had a much higher protein-capturing capacity than the naked MNPs (56% versus 6%). Moreover, MNPPBA almost thoroughly captured the tested enzymes, i.e., urease, invertase, and alkaline phosphatase, from enzyme solutions. Based on MNPPBA, a soil enzyme assay method was developed by integration of enzyme capture, magnetic separation and trace enzyme analysis. The method was successfully applied in determining trace enzyme activity in rhizosphere soil. This study provides a strategy to sensitively determine soil enzyme activity for mechanistic investigation of soil fertility and plant-microbiome interaction.
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Project description:The continuous imbalance of the diabetic wound microenvironment is an important cause of chronic nonhealing, which manifests as a vicious cycle between excessive accumulation of reactive oxygen species (ROS) and abnormal healing. Regulating the microenvironment by suppressing wound inflammation, oxidative stress, and bacterial infection is a key challenge in treating diabetic wounds. In this study, ROS-responsive hydrogels are developed composed of silk fibroin methacrylated (SFMA), modified collagen type III (rCol3MA), and lipid nanoparticles (LNPs). The newly designed hydrogel system demonstrated stable physicochemical properties and excellent biocompatibility. Moreover, the release of antimicrobial peptide (AMP) and puerarin (PUE) demonstrated remarkable efficacy in eradicating bacteria, regulating inflammatory responses, and modulating vascular functions. This multifunctional hydrogel is a simple and efficient approach for the treatment of chronic diabetic infected wounds and holds tremendous potential for future clinical applications.
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Project description:The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy.
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Project description:Two important features are required for promising radiosensitizers: one is selective tumor cell targeting to enhance the therapeutic outcome via lethal DNA damage and the other is rapid clearance to enable excellent biocompatibility for potential clinical application. Herein, ultrasmall gold nanoparticles (Au NPs) with diameter smaller than 5 nm were prepared and covered with a multifunctional peptide to endow them with selective tumor cell uptake capability. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing toxicity and rapid renal clearance in vivo. Methods: A responsive peptide (Tat-R-EK) consists of three build blocks were used: a cell and even nuclear penetrating block derived from human immunodeficiency virus-1 transactivator of transcription protein (Tat), an cathepsin B cleavable linker, and a zwitterionic antifouling block. Ultrasmall Au NPs were prepared and then covered by the peptide via the Au-S bonds between gold and thiol groups from cysteine. The morphology, colloidal stability and the responsiveness of obtained Au@Tat-R-EK NPs were studied using transmittance electron microscopy and dynamic laser scattering. The selective cancer cell uptake and accumulation of Au@Tat-R-EK NPs in cancer tissue were studied via ICP-MS in vitro and in vivo, respectively. The cytotoxicity of Au@Tat-R-EK NPs on HepG2 cancer cells was evaluated in terms of cell viability, DNA damage, intracellular reactive oxygen species generation, and apoptosis analysis. Finally, the biocompatibility and tumor destruction ability against orthotopic LM3 liver cancers were verified in vivo. Results: Multifunctional peptide modified ultrasmall Au NPs were successfully prepared. The Au NPs exhibited enough colloidal stability and cathepsin B-responsive surface change, leading to selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Combined with X-ray irradiation, the responsive Au NPs demonstrated superior radio-sensitizing cytotoxicity in vitro and therapeutic outcome on mouse liver cancer in vivo. The ultrasmall size enables rapid clearance of the Au NPs, guarantees the biocompatibility in vivo for potential clinical applications. Conclusion: Some obstacles faced by the Au NPs-based radiotherapy, such as short circulation half-life, non-specific distribution, slow clearance and low radio-sensitizing effect, were effective solved through rational design of the smart nanomedicine. This work provides new insight in designing tumor microenvironment-responsive nanomedicine in cancer radiotherapy.
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Project description:AbstractIn this work, 2-(2-aminoethoxy) ethanol-blocked phenylboronic acid-functionalized magnetic nanoparticles (blocked PMNPs) were fabricated for selective enrichment of different types of saccharides. The phenylboronic acid was designed for capturing the cis-diols moieties on saccharides molecules, and the 2-(2-aminoethoxy) ethanol can deplete the nonspecific absorption of peptides and proteins which always coexisted with saccharides. For mass spectrometry analysis, the PMNPs bound saccharides can be directly applied onto the MALDI plate with matrix without removing the PMNPs. By PMNPs, the simple saccharide (glucose) could be detected in pmol level. The complex saccharides can also be reliably purified and analyzed; 16 different N-glycans were successfully identified from ovalbumin, and the high-abundance N-glycans can be detected even when the ovalbumin was in very low concentration (2 μg). In human milk, ten different oligosaccharides were identified, and the lactose can still be detected when the human milk concentration was low to 0.01 μL.Graphical abstract
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