Bone-drug targeting therapies using nanoparticles based on targeting ligands remain challenging due to their uptake clearance at non-target sites such as the liver, kidney, and spleen. Furthermore, the distribution sites of nanoparticles in bones have not been fully investigated, thus halting the development of more effective bone metastasis treatment strategies. In this study, we developed nanoparticles self-assembled from cholesterol-terminated, polyethylene glycol-conjugated, aspartic acid (Asp)-modified polyamidoamine dendrimer (Asp-PAMAM-Micelles) with targeting to active bone turnover sites associated with bone metastasis pathogenesis. On analysis through whole-body single photon emission computed tomography/computed tomography (SPECT/CT) imaging, In-Asp-PAMAM-Micelles showed high specificity to active bone turnover sites (especially the joints in the lower limbs, shoulder, and pelvis) after intravenous injection in mice. The lower limb bone uptake clearance for In-Asp-PAMAM-Micelles encapsulating paclitaxel (PTX) was 3.5-fold higher than that for In-unmodified PAMAM-Micelles (PTX). H-PTX encapsulated Asp-PAMAM-Micelles effectively accumulated in the lower limb bones in a similar manner as the In-Asp-PAMAM-Micelles (PTX). In a bone metastatic tumor mouse model, the tumor growth in the lower limb bones was significantly inhibited by injection of Asp-PAMAM-Micelles (PTX) compared to unmodified PAMAM-Micelles (PTX). Our results demonstrate that Asp-PAMAM-Micelles are sophisticated drug delivery systems for highly potent targeting to active bone turnover sites.
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http://dx.doi.org/10.1016/j.ejpb.2020.10.001 | DOI Listing |
Am J Sports Med
January 2025
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Background: Knee injuries resulting in purely cartilaginous defects are rare, and controversy remains regarding the reliability of chondral-only fixation.
Purpose: To systematically review the literature for fixation methods and outcomes after primary fixation of chondral-only defects within the knee.
Study Design: Systematic review; Level of evidence, 5.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China.
Chrysoeriol (CHE) is a naturally occurring compound with established anti-inflammatory and anti-tumor effects. This study examines its potential role in regulating osteoclast differentiation and activity, both of which are crucial for bone remodeling. Computational docking revealed high binding affinity between CHE and RANKL, specifically at the Lys-181 residue of RANKL, suggesting potential inhibitory interactions on osteoclastogenesis.
View Article and Find Full Text PDFBMC Oral Health
January 2025
Beijing Institute of Dental Research, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
Background: Low-intensity pulsed ultrasound (LIPUS) has been used as an effective noninvasive method for treating fractures and osteoarthrosis, but the application in the field of oral implantation is in its infancy. This study aimed to clarify the effect and mechanism of LIPUS on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and implant osseointegration, and to provide an experimental basis for future clinical applications.
Methods: Dental implants were inserted into Wistar rat femurs, and LIPUS was performed for 4 weeks.
J Immunother Cancer
January 2025
Center for Translational Research in Hematologic Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, Texas, USA
Background: Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy.
View Article and Find Full Text PDFJ Hand Ther
January 2025
Department of Plastic and Hand Surgery, Inselspital Bern, University of Bern, Bern, Switzerland.
Background: Non-invasiveness and comfort are crucial in the conservative management of distal radius and scaphoid fractures. While fiberglass casts are standard, three-dimensional (3D)-printed orthoses offer a promising alternative.
Purpose: To compare patient experiences, safety perceptions, and satisfaction between a 3D orthosis and fiberglass cast for distal radius or scaphoid fractures.
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