ArticlePloS one2014
Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 54 citations in OpenAlex.
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- Drug-loaded erythrocytes: Modern approaches for advanced drug delivery for clinical use.Heliyon · 2024Review
- Unveiling the Immune Microenvironment's Role in Breast Cancer: A Glimpse into Promising Frontiers.International journal of molecular sciences · 2023Review
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- Advanced strategies to evade the mononuclear phagocyte system clearance of nanomaterials.Exploration (Beijing, China) · 2023Review
- Layer-by-Layer Surface Modification of Alendronate-Loaded Polyester Microparticles-Enabling Protein Immobilization.Polymers · 2022Article
- Periapical status in patients affected by osteoporosis: A retrospective clinical study.Clinical and experimental dental research · 2022Article
- Cancer immune therapy using engineered ‛tail-flipping' nanoliposomes targeting alternatively activated macrophages.Nature communications · 2022Article
- Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System.Drug design, development and therapy · 2022Article
- Red blood cells: The metamorphosis of a neglected carrier into the natural mothership for artificial nanocarriers.Advanced drug delivery reviews · 2021Review
- Zoledronate alters natural progression of tissue-engineered vascular grafts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers.Annual review of biomedical engineering · 2021Article
- Erythrocytes as Carriers: From Drug Delivery to Biosensors.Pharmaceutics · 2020Review
- Preclinical evaluation of an innovative anti-TAM approach based on zoledronate-loaded erythrocytes.Drug delivery and translational research · 2018Article
- Nanomedicine Strategies to Target Tumor-Associated Macrophages.International journal of molecular sciences · 2017Review
- Tumor-Associated Macrophage-Mediated Targeted Therapy of Triple-Negative Breast Cancer.Molecular pharmaceutics · 2016Article
- Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors.Oncoimmunology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bisphosphonates, besides being important drugs for the treatment of various bone diseases, could also be used to induce apoptosis in macrophage-like and cancer cells. However, their activity in vivo is limited by a short plasma half-life and rapid uptake within bone. Therefore, several delivery systems have been proposed to modify their pharmacokinetic profile and biodistribution. Among these, red blood cells (RBCs) represent one of the most promising biological carriers. The aim of this study was to select the best performing compound among Clodronate, Pamidronate, Ibandronate and Zoledronate in killing macrophages and to investigate RBCs as innovative carrier system to selectively target bisphosphonates to macrophages. To this end, the encapsulation of the selected bisphosphonates in autologous RBCs as well as the effect on macrophages, both in vitro and in vivo were studied. This work shows that, among the tested bisphosphonates, Zoledronate has proven to be the most active molecule. Human and murine RBCs have been successfully loaded with Zoledronate by a procedure of hypotonic dialysis and isotonic resealing, obtaining a dose-dependent drug entrapment with a maximal loading of 7.96±2.03, 6.95±3.9 and 7.0±1.89 µmoles of Zoledronate/ml of packed RBCs for human, Swiss and Balb/C murine RBCs, respectively. Engineered RBCs were able to detach human and murine macrophages in vitro, leading to a detachment of 66±8%, 67±8% and 60.5±3.5% for human, Swiss and Balb/C RBCs, respectively. The in vivo efficacy of loaded RBCs was tested in Balb/C mice administering 59 µg/mouse of RBC-encapsulated Zoledronate. By a single administration, depletion of 29.0±16.38% hepatic macrophages and of 67.84±5.48% spleen macrophages was obtained, confirming the ability of encapsulated Zoledronate to deplete macrophages in vivo. In conclusion, RBCs loaded with Zoledronate should be considered a suitable system for targeted delivery to macrophages, both in vitro and in vivo.
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