Bone morphogenetic protein-2 (BMP-2), a growth factor that induces osteoblast differentiation and promotes bone regeneration, has been extensively investigated in bone tissue engineering. The peptides of bioactive domains, corresponding to residues 73-92 of BMP-2 become an alternative to reduce adverse side effects caused by the use of high doses of BMP-2 protein. In this study, BMP-2 peptide functionalized mesoporous silica nanoparticles (MSNs-pep) were synthesized by covalently grafting BMP-2 peptide on the surface of nanoparticles via an aminosilane linker, and dexamethasone (DEX) was then loaded into the channel of MSNs to construct nanoparticulate osteogenic delivery systems (DEX@MSNs-pep). The in vitro cell viability of MSNs-pep was tested with bone mesenchymal stem cells (BMSCs) exposure to different particle concentrations, revealing that the functionalized MSNs had better cytocompatibility than their bare counterparts, and the cellular uptake efficiency of MSNs-pep was remarkably larger than that of bare MSNs. The in vitro results also show that the MSNs-pep promoted osteogenic differentiation of BMSCs in terms of the levels of alkaline phosphatase (ALP) activity, calcium deposition, and expression of bone-related protein. Moreover, the osteogenic differentiation of BMSCs can be further enhanced by incorporating of DEX into MSNs-pep. After intramuscular implantation in rats for 3 weeks, the computed tomography (CT) images and histological examination indicate that this nanoparticulate osteogenic delivery system induces effective osteoblast differentiation and bone regeneration in vivo. Collectively, the BMP-2 peptide and DEX incorporated MSNs can act synergistically to enhance osteogenic differentiation of BMSCs, which have potential applications in bone tissue engineering.
Surface fuctionalization plays a crucial role in developing efficient nanoparticulate drug-delivery systems by improving their therapeutic efficacy and minimizing adverse effects. Here we propose a simple layer-by-layer self-assembly technique capable of constructing mesoporous silica nanoparticles (MSNs) into a pH-responsive drug delivery system with enhanced efficacy and biocompatibility. In this system, biocompatible polyelectrolyte multilayers of alginate/chitosan were assembled on MSN's surface to achieve pH-responsive nanocarriers. The functionalized MSNs exhibited improved blood compatibility over the bare MSNs in terms of low hemolytic and cytotoxic activity against human red blood cells. As a proof-of-concept, the anticancer drug doxorubicin (DOX) was loaded into nanocarriers to evaluate their use for the pH-responsive drug release both in vitro and in vivo. The DOX release from nanocarriers was pH dependent, and the release rate was much faster at lower pH than that of at higher pH. The in vitro evaluation on HeLa cells showed that the DOX-loaded nanocarriers provided a sustained intracellular DOX release and a prolonged DOX accumulation in the nucleus, thus resulting in a prolonged therapeutic efficacy. In addition, the pharmacokinetic and biodistribution studies in healthy rats showed that DOX-loaded nanocarriers had longer systemic circulation time and slower plasma elimination rate than free DOX. The histological results also revealed that the nanocarriers had good tissue compatibility. Thus, the biocompatible multilayers functionalized MSNs hold the substantial potential to be further developed as effective and safe drug-delivery carriers.
Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.
The bio-integrated electronics industry is booming and becoming more integrated with biological tissues. To successfully integrate with the soft tissues of the body (eg. skin), the material must possess many of the same properties including compliance, toughness, elasticity, and tear resistance. In this work, we prepare mechanically and biologically skin-like materials (PSeD-U elastomers) by designing a unique physical and covalent hybrid crosslinking structure. The introduction of an optimal amount of hydrogen bonds significantly strengthens the resultant elastomers with 11 times the toughness and 3 times the strength of covalent crosslinked PSeD elastomers, while maintaining a low modulus. Besides, the PSeD-U elastomers show nonlinear mechanical behavior similar to skins. Furthermore, PSeD-U elastomers demonstrate the cytocompatibility and biodegradability to achieve better integration with tissues. Finally, piezocapacitive pressure sensors are fabricated with high pressure sensitivity and rapid response to demonstrate the potential use of PSeD-U elastomers in bio-integrated electronics.
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