Parkerpridgen8652

NanoHA was tightly adhered to the tubule walls, filling the entire tubule volume after 7 days. The results of this study demonstrate the mode of action of the amorphous calcium magnesium phosphate particles in occluding exposed dentin tubules. Interaction with saliva and transformation of the particles within the tubules inducing further mineralization indicate that the particles may be used as an effective treatment to reduce dentin hypersensitivity.The purpose of developing novel anticancer drug delivery systems (DDSs) is to efficiently carry and release drugs into cancer cells and minimize side effects. In this work, based on hollow mesoporous silica nanoparticle (HMSN) and the charge-reversal property, a pH/GSH-dual-sensitive DDS named DOX@HMSN-SS-PLL(cit) was reported. HMSN encapsulated DOX with high efficacy and was then covered by the "gatekeeper" β-cyclodextrin (β-CD) through the glutathione (GSH)-sensitive disulfide bond. Thereafter, adamantine-blocked citraconic-anhydride-functionalized poly-l-lysine (PLL(cit)-Ad) was decorated on the surface of the particles via host-guest interaction. The negatively charged carriers were stable in the neutral environment in vivo and could be effectively transported to the tumor site. The surface charge of the nanoparticles could be reversed in the weakly acidic environment, which increased the cellular uptake ability of the carriers by the cancer cells. After cellular internalization, β-CD can be removed by breakage of the disulfide bond in the presence of a high concentration of GSH, leading to DOX release. The preparation process of the carriers was monitored. The charge-reversal capability and the controlled drug-release behavior of the carriers were also investigated. In vitro and in vivo experiments demonstrated the excellent cancer therapy effect with low side effects of the carriers. It is expected that dual-sensitive DOX@HMSN-SS-PLL(cit) could play an important role in cancer therapy.Collagen type II is a promising material to repair cartilage defects since it is a major component of articular cartilage and plays a key role in chondrocyte function. this website This study investigated the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) embedded within a 31 collagen type I to II blend (Col I/II) hydrogel or an all collagen type I (Col I) hydrogel. Glycosaminoglycan (GAG) production in Col I/II hydrogels was statistically higher than that in Col I hydrogels or pellet culture, and these results suggested that adding collagen type II promoted GAG production. Col I/II hydrogels had statistically lower alkaline phosphatase (AP) activity than pellets cultured in a chondrogenic medium. The ability of MSCs encapsulated in Col I/II hydrogels to repair cartilage defects was investigated by creating two cartilage defects in the femurs of rabbits. After 13 weeks, histochemical staining suggested that Col I/II blend hydrogels provided favorable conditions for cartilage repair. Histological scoring revealed a statistically higher cartilage repair score for the Col I/II hydrogels compared to either the Col I hydrogels or empty defect controls. Results from this study suggest that there is clinical value in the cartilage repair capabilities of our Col I/II hydrogel with encapsulated MSCs.Despite successes in breast cancer treatment, the incidence of metastasis, drug resistance, and toxicity limit the efficacy of current therapeutic modalities. Herein, by designing lactoferrin-doxorubicin-mesoporous maghemite nanoparticles (Lf-Doxo-MMNPs), we not only provided targeted drug delivery (TDD), but also enabled chemotherapy/magnetic field/photothermal (chemo/MF/PTT) combination therapy to mitigate breast cancer proliferation and metastasis. After synthesizing Lf-Doxo-MMNPs by hydrothermal method and characterizing their features, we examined their effect on the body weight, tumor growth inhibition (TGI), tumor size, Doxo and iron biodistribution, histopathology of metastatic lung tissue, heart tissue, and breast tumor, cell death mechanisms, and metastatic gene expression. The results showed that Lf-Doxo-MMNPs, in addition to enhancing anticancer effects in vitro, resulted in a significant increase in body weight, TGI, and targeted drug delivery (TDD). In addition to the significant impacts of Lf-Doxo-MMNPs on the reduction of cancer cell proliferation, their application in chemo/MF/PTT combination therapy has a remarkable effect on the antimetastatic activities against breast tumors. Indeed, chemo/MF/PTT combination therapy exhibited the most reduction in metastatic activity of breast cancer based on controlling C-X-C motif chemokine ligand 12 (CXCL12) and chemokine receptor 7 (CXCR7) mRNA expression. In conclusion, the promising results of Doxo accumulation, reduced cancer cell proliferation, and inhibition of metastatic mRNA expression indicated that MMNPs provide a potential platform for combined therapeutic approaches.The mechanism by which cationic polymers containing titratable amines mediate effective endosomal escape and cytosolic delivery of nucleic acids is not well understood despite the decades of research devoted to these materials. Here, we utilize multiple assays investigating the endosomal escape step associated with plasmid delivery by polyethylenimine (PEI) and poly(β-amino esters) (PBAEs) to improve the understanding of how these cationic polymers enable gene delivery. To probe the role of these materials in facilitating endosomal escape, we utilized vesicle membrane leakage and extracellular pH modulation assays to demonstrate the influence of polymer buffering capacity and effective pKa on the delivery of the plasmid DNA. Our results demonstrate that transfection with PBAEs is highly sensitive to the effective pKa of the overall polymer, which has broad implications for transfection. In more acidic environments, PBAE-mediated transfection was inhibited, while PEI was relatively unaffected. In neutral to basic environments, PBAEs have high buffering capacities that led to dramatically improved transfection efficacy. The cellular uptake of polymeric nanoparticles overall was unchanged as a function of pH, indicating that microenvironmental acidity was important for downstream intracellular delivery efficiency. Overall, this study motivates the use of polymer chemical characteristics, such as effective pKa values, to more efficiently evaluate new polymeric materials for enhanced intracellular delivery characteristics.