Supercritical CO2-assisted fabrication of CM-PDA/SF/nHA nanofibrous scaffolds for bone regeneration and chemo-photothermal therapy against osteosarcoma.

Concurrent treatment of tumor recurrence and bone defects after surgical resection of osteosarcoma remains a clinical challenge. Combination therapy based on local drug delivery systems shows great promise in the treatment of osteosarcoma. In this study, curcumin modified polydopamine nanoparticle loaded silk fibroin doped with nano-hydroxyapatite (CM-PDA/SF/nHA) nanofibrous scaffolds were developed to induce bone defect regeneration and chemo-photothermal synergistic effects against osteosarcoma. These scaffolds exhibited good photothermal conversion efficiency and photostability. Moreover, the results of ALP staining and alizarin red S (ARS) staining indicated that the CM-PDA/SF/1%nHA scaffolds had the most obvious promotion effect on early osteogenic differentiation. The results of in vitro and in vivo anti-osteosarcoma activity showed that the CM-PDA/SF/1%nHA scaffolds exhibited higher anti-osteosarcoma activity compared to the control and SF scaffolds. In addition, the CM-PDA/SF/1%nHA scaffolds could promote the proliferation and differentiation of bone marrow mesenchymal stem cells in vitro and new bone production in vivo. Thus, these results suggested that the CM-PDA/SF/1%nHA scaffolds could improve bone defect regeneration and achieve chemo-photothermal synergistic effects against osteosarcoma.

3D-Printed Piezoelectric Scaffolds with Shape Memory Polymer for Bone Regeneration.

The application of piezoelectric nanoparticles with shape memory polymer (SMP) to 3D-printed piezoelectric scaffolds for bone defect repair is an attractive research direction. However, there is a significant difference in dielectric constants between the piezoelectric phase and polymer phase, limiting the piezoelectric property. Therefore, novel piezoelectric acrylate epoxidized soybean oil (AESO) scaffolds doped with piezoelectric Ag-TMSPM-pBT (ATP) nanoparticles (AESO-ATP scaffolds) are prepared via digital light procession 3D-printing. The Ag-TMSPM-pBT nanoparticles improve the piezoelectric properties of the AESO scaffolds by TMSPM covalent functionalization and conductive Ag nanoparticles. The AESO scaffolds doped with 10 wt% Ag-TMSPM-pBT nanoparticles (AESO-10ATP scaffolds) exhibit promising piezoelectrical properties, with a piezoelectric coefficient (d33) of 0.9 pC N-1 and an output current of 146.4 nA, which are close to the piezoelectric constants of bone tissue. In addition, these scaffolds exhibit good shape memory function and can quickly recover their original shape under near-infrared (NIR) light irradiation. The results of osteogenesis capability evaluation indicate that the AESO-10ATP scaffolds can promote osteogenic differentiation of BMSCs in vitro and bone defect repair in vivo, indicating the 3D-printed AESO-10ATP piezoelectric scaffolds may have great application potential for bone regeneration.

Multifunctional nanoparticles for the treatment and diagnosis of osteosarcoma.

Osteosarcoma (OS) is a common primary malignant bone tumor in adolescents. Currently, the commonly used treatment strategies for OS include surgery, chemotherapy and radiotherapy. However, these methods have some problems that cannot be ignored, such as postoperative sequelae and severe side effects. Therefore, in recent years, researchers have been looking for other means to improve the treatment or diagnosis effect of OS and increase the overall survival rate of patients. With the development of nanotechnology, nanoparticles (NPs) have presented excellent properties in improving the therapeutic efficacy of drugs for OS. Nanotechnology makes it possible for NPs to combine various functional molecules and drugs to achieve multiple therapeutic effects. This review presents the important properties of multifunctional NPs for the treatment and diagnosis of OS and focuses on the research progress of common NPs applied for drug or gene delivery, phototherapy and diagnosis of OS, such as carbon-based quantum dots, metal, chitosan and liposome NPs. Finally, the promising prospects and challenges of developing multifunctional NPs with enhanced efficacy are discussed, which lays the foundation and direction for improving the future therapeutic and diagnostic methods of OS.

Biomineralization improves the stability of a Streptococcus pneumoniae protein vaccine at high temperatures.

Aim: Protein vaccines have been the focus of research for vaccine development due to their safety record and facile production. Improving the stability of proteins is of great significance to the application of protein vaccines. Materials & methods: Based on the proteins pneumolysin and DnaJ of Streptococcus pneumoniae, biomineralization was carried out to prepare protein nanoparticles, and their thermal stability was tested both in vivo and in vitro. Results: Mineralized nanoparticles were formed successfully and these calcium phosphate-encapsulated proteins were resistant to proteinase K degradation and were thermally stable at high temperatures. The mineralized proteins retained the immunoreactivity of the original proteins. Conclusion: Mineralization technology is an effective means to stabilize protein vaccines, presenting a safe and economical method for vaccine administration.

Streptococcus pneumoniae Endopeptidase O Promotes the Clearance of Staphylococcus aureus and Streptococcus pneumoniae via SH2 Domain-Containing Inositol Phosphatase 1-Mediated Complement Receptor 3 Upregulation.

Increasing evidences demonstrate that microorganism and their products protect against bacterial and viral pathogens through various mechanisms including immunomodulation. Streptococcus pneumoniae endopeptidase O (PepO), a pneumococcal virulence protein, has been proven to enhance the phagocytosis of Staphylococcus aureus and Streptococcus pneumoniae by macrophages in our previous study, where we detected the down regulation of SH2 domain-containing inositol phosphatase 1 (SHIP1) and the up regulation of complement receptor 3 (CR3) in PepO-stimulated macrophages. In the present study, using SHIP1 over-expression plasmid and CR3 siRNA, we proved that the down regulation of SHIP1 and the up regulation of CR3 mediate the enhanced phagocytosis of S. aureus and S. pneumoniae by PepO-stimulated macrophages. The down regulation of SHIP1 also mediates the up regulation of CR3. To further determine whether PepO protects against respiratory pathogens, we constructed a mouse model with intranasal infection of S. aureus or S. pneumoniae and found that PepO significantly promoted their clearance. The down regulation of SHIP1 and the up regulation of CR3 also play a role in this process. This study provides a new preventive and therapeutic option for respiratory infectious diseases and lays the theoretical basis for the development of PepO as an immunomodulation agent.

Engineering detoxified pneumococcal pneumolysin derivative ΔA146PLY for self-biomineralization of calcium phosphate: Assessment of their protective efficacy in murine infection models.

Vaccine design ushered in the era of nanotechnology, as the vaccine is being developed toward particulate formulation. We have previously shown that the attenuated pneumolysin mutant (ΔA146PLY) was a safe and effective pneumococcal vaccine candidate. Here, to further optimize the formulation, we fused calcium phosphate (CaP) binding domains with ΔA146PLY so that the biocompatible CaP can mineralize with the protein automatically, allowing simple production of nanoparticle antigen during preparation. We fabricated four different nanoparticles, and then we compared the characteristics of different CaP-ΔA146PLY nanoparticles and demonstrated the influence of CaP binding domains on the size, shape and surface calcium content of the nanoparticles. It was found that these self-biomineralized CaP-ΔA146PLY nanoparticles varied in their capacity to induce BMDCs and splenocytes production of cytokines. We further demonstrated that, compared to free proteins, nanoparticle antigens induced more efficient humoral and cellular immune responses which was strong enough to protect mice from both pneumonia and sepsis infection. Also, the integration of CaP to protein has no significant impairment on body weight of animals, and subcutaneous injection of ΔA146PLY-peptides@CaP nanoparticles did not lead to permanent formation of nodules in the skin relative to Alum adjuvant formulated antigens. Together, our data sufficiently suggest that soluble ΔA146PLY vaccine candidate could be processed into nanoparticles by self-biomineralization of CaP, the immunogenicity of which could be efficiently improved by the CaP binding domains and biomineralization.