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

One-Pot Synthesis of MoS₂ Nanoflakes with Desirable Degradability for Photothermal Cancer Therapy

Developing biodegradable photothermal agent holds great significance for potential clinical translation of photothermal therapy. In the current study, one-pot hydrothermal synthesis of MoS₂ nanoflakes with desirable degradation capability was presented. The participation of poly­(acrylic acid) (PAA) in hydrothermal process could not only facilitate the modification of polyethylene glycol (PEG), but also bestow degradability to the prepared MoS₂ nanoflakes. Moreover, the PEGylated hybrid nanoflakes (MoS₂–PPEG) also exhibited excellent stability in various medium and outstanding photothermal properties. Interestingly, MoS₂–PPEG behaved distinctly different degradation rate in diverse condition. The rapid degradation of MoS₂–PPEG was observed in neutral pH solution, whereas much slower degradation occurred in an acidic tumor microenvironment. Furthermore, data indicated that the major degradation product of MoS₂–PPEG was water-soluble Mo-based ion. Meanwhile, the good in vitro biocompatibility of MoS₂–PPEG was also confirmed in terms of cytotoxicity and hemolysis. With favorable photothermal performance, MoS₂–PPEG can efficiently killing cancer cells in vitro and suppress the tumor growth in vivo. More importantly, the gradual decreasing content of MoS₂–PPEG in organs and detectable Mo element in urine of mice suggested that the degradability of MoS₂–PPEG might facilitate its excretion to some degree. Hence, the degradable MoS₂ nanoflakes prepared by one-pot hydrothermal routine may provide insight for further biomedical applications of inorganic photothermal agent

Dual-Responsive Mesoporous Silica Nanoparticles Mediated Codelivery of Doxorubicin and Bcl‑2 SiRNA for Targeted Treatment of Breast Cancer

The combination of chemotherapy and gene therapy could induce the enhanced therapeutic efficacy in the cancer therapy. To achieve this goal, a new mesoporous silica nanoparticles (MSNs)-based codelivery system was developed for targeted simultaneous delivery of doxorubicin (DOX) and Bcl-2 small interfering RNA (siRNA) into breast cancer cells. The multifunctional MSNs (MSNs-PPPFA) were prepared by modification of polyethylenimine–polylysine copolymers (PEI-PLL) via the disulfide bonds, to which a targeting ligand folate-linked poly­(ethylene glycol) (FA-PEG) was conjugated. The multifunctional MSNs-PPPFA nanocarrier has the ability to encapsulate DOX into the mesoporous channels of MSNs, while simultaneously carrying siRNA via electrostatic interaction between cationic MSNs-PPPFA and anionic siRNA. The resulting MSNs-PPPFA nanoparticles were characterized with various techniques. The drug release results reveal that DOX released from DOX-loaded MSNs-PPPFA are both pH- and redox-responsive, and the results of cell viability and hemolysis assays show that the functional nanocarrier has excellent biocompatibility. Importantly, the folate-conjugated MSNs-PPPFA showed significantly enhanced intracellular uptake in the folate receptor overexpressed MDA-MB-231 breast cancer cells than nontargeted counterparts and thus results in more DOX and siRNA being codelivered into the cells. Furthermore, the delivery of Bcl-2 siRNA obviously downregulate the Bcl-2 protein expression, and thus targeted codelivery of DOX and Bcl-2 siRNA by DOX@MSNs-PPPFA/Bcl-2 siRNA in MDA-MB-231 cells could induce remarkable cell apoptosis as indicated by the results of cell viability and cell apoptosis assays. These results indicate that the constructed DOX@MSNs-PPPFA/Bcl-2 siRNA codelivery system is promising for targeted treatment of breast cancer

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

Marriage of Albumin–Gadolinium Complexes and MoS₂ Nanoflakes as Cancer Theranostics for Dual-Modality Magnetic Resonance/Photoacoustic Imaging and Photothermal Therapy

The construction of safe and stable theranostics is beneficial to realize simultaneous cancer diagnosis and treatment. In this study, bovine serum albumin–gadolinium (BSA–Gd) complexes and MoS₂ nanoflakes (MoS₂–Gd–BSA) were successfully married as cancer theranostics for dual-modality magnetic resonance (MR)/photoacoustic (PA) imaging and photothermal therapy (PTT). BSA–Gd complexes were prepared by the biomineralization method and then conjugated with MoS₂ nanoflakes via an amide bond. The as-prepared MoS₂–Gd–BSA possessed a good photostability and photothermal effect. The cytotoxicity assessment and hemolysis assay suggested the excellent biocompatibility of MoS₂–Gd–BSA. Meanwhile, MoS₂–Gd–BSA could not only achieve in vivo MR/PA dual-modality imaging of xenograft tumors, but also effectively kill cancer cells in vitro and ablate the xenograft tumors in vivo upon 808 nm laser illumination. The biodistribution and histological evaluations indicated the negligible toxicity of MoS₂–Gd–BSA both in vitro and in vivo. Thus, our results substantiated the potential of MoS₂–Gd–BSA for cancer theranostics