Au/Polypyrrole@Fe₃O₄ Nanocomposites for MR/CT Dual-Modal Imaging Guided-Photothermal Therapy: An <i>in Vitro</i> Study

Construction of multifunctional nanocomposites as theranostic platforms has received considerable biomedical attention. In this study, a triple-functional theranostic agent based on the cointegration of gold nanorods (Au NRs) and superparamagnetic iron oxide (Fe₃O₄) into polypyrrole was developed. Such a theranostic agent (referred to as Au/PPY@Fe₃O₄) not only exhibits strong magnetic property and high near-infrared (NIR) optical absorbance but also produces high contrast for magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Importantly, under the irradiation of the NIR 808 nm laser at the power density of 2 W/cm² for 10 min, the temperature of the solution containing Au/PPY@Fe₃O₄ (1.4 mg/mL) increased by about 35 °C. Cell viability assay showed that these nanocomposites had low cytotoxicity. Furthermore, an <i>in vitro</i> photothermal treatment test demonstrates that the cancer cells can be efficiently killed by the photothermal effects of the Au/PPY@Fe₃O₄ nanocomposites. In summary, this study demonstrates that the highly versatile multifunctional Au/PPY@Fe₃O₄ nanocomposites have great potential in simultaneous multimodal imaging-guided cancer theranostic applications

BMP‑2 Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells

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

Effect of pH-Responsive Alginate/Chitosan Multilayers Coating on Delivery Efficiency, Cellular Uptake and Biodistribution of Mesoporous Silica Nanoparticles Based Nanocarriers

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 <i>in vitro</i> and <i>in vivo</i>. 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 <i>in vitro</i> 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

Electrophoretic Deposition of Dexamethasone-Loaded Mesoporous Silica Nanoparticles onto Poly(l‑Lactic Acid)/Poly(ε-Caprolactone) Composite Scaffold for Bone Tissue Engineering

The incorporation of microcarriers as drug delivery vehicles into polymeric scaffold for bone regeneration has aroused increasing interest. In this study, the aminated mesoporous silica nanoparticles (MSNs-NH₂) were prepared and used as microcarriers for dexamethasone (DEX) loading. Poly­(l-lactic acid)/poly­(ε-caprolactone) (PLLA/PCL) nanofibrous scaffold was fabricated via thermally induced phase separation (TIPS) and served as template, onto which the drug-loaded MSNs-NH₂ nanoparticles were deposited by electrophoretic deposition (EPD). The physicochemical and release properties of the prepared scaffolds (DEX@MSNs-NH₂/PLLA/PCL) were examined, and their osteogenic activities were also evaluated through in vitro and in vivo studies. The release of DEX from the scaffolds revealed an initial rapid release followed by a slower and sustained one. The in vitro results indicated that the DEX@MSNs-NH₂/PLLA/PCL scaffold exhibited good biocompatibility to rat bone marrow-derived mesenchymal stem cells (BMSCs). Also, BMSCs cultured on the DEX@MSNs-NH₂/PLLA/PCL scaffold exhibited a higher degree of osteogenic differentiation than those cultured on PLLA/PCL and MSNs-NH₂/PLLA/PCL scaffolds, in terms of alkaline phosphatase (ALP) activity, mineralized matrix formation, and osteocalcin (OCN) expression. Furthermore, the in vivo results in a calvarial defect model of Sprague–Dawley (SD) rats demonstrated that the DEX@MSNs-NH₂/PLLA/PCL scaffold could significantly promote calvarial defect healing compared with the PLLA/PCL scaffold. Thus, the EPD technique provides a convenient way to incorporate osteogenic agents-containing microcarriers to polymer scaffold, and thus, prepared composite scaffold could be a potential candidate for bone tissue engineering application due to its capacity for delivery of osteogenic agents