Selectively induced death of macrophages in the synovial lining of murine knee joints using 10B-liposomes and boron neutron capture synovectomy

Abstract

Objective: To investigate whether macrophages in the synovial lining can be selectively eliminated by local administration of an improved boron-10 ( 10 B) containing liposome formulation combined with neutron irradiation (boron neutron capture synovectomy [BNCS]). Methods: Disodium dodecahydrododecaborate (Na 2 10 B 12 H 12 ) was encapsulated into unilamellar liposomes ( 10 Bliposomes). 10 B-liposomes were injected into the mouse knee joint. Amounts of 10 B in synovial tissue were measured over time using inductively coupled plasma-optical emission spectrometry (ICP-OES). Arthritis was induced in knee joints of mice. Joint inflammation and cartilage destruction was measured using histology. Results: When a 10 ml 10 B-liposome solution (containing 40 mg 10 B) was injected into the murine knee joint, high concentrations of 10 B were measured in macrophages in the synovial lining (At 24 h 306+226 mg . g 71 macrophages). Completing the BNCS by neutron irradiation of the legs 24 h after 10 B-liposome injection showed a clear selective depletion of macrophages in synovial lining of the knee joints. An estimated total physical dose of 13+9 Gy was given to the macrophages. When arthritis was induced in the macrophage-depleted joints, swelling of the knee was significantly lower as compared to the controls (53% and 79% lower at days 1 and 3, respectively). Histology confirmed the influx of inflammatory cells was strongly decreased and severe cartilage destruction was almost completely prevented. Conclusion: BNCS using an improved 10 B-containing liposome formulation can cause selective depletion of macrophages in the synovial lining of murine knee joints. As a result of this proof-of principle, future applications are recommended.

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy

“…In the early 1990s, the application of liposomal boron delivery systems in BNCT was first investigated, 75 and since then, numerous outstanding studies have been conducted on the use of liposomes in BNCT. 76 Hawthorne and colleagues 77 synthesized a monolayer liposome that exhibits stable binding with K[nido-7-CH 3 (CH 2 ) 15 -7,8-C 2 B 9 H 11 ] (MAC) and Na 3 [1-(2′-B 10 H 9 )-2-NH 3 B 10 H 8 ] (TAC) within the bilayer membrane. They proposed that the incorporation of these amphiphilic nitrogen−carbon−boron compounds into the bilayer facilitates the selective accumulation of high boron concentrations in tumors.…”

“…Given this, liposomal delivery systems have attracted considerable attention as an attractive intelligent technology for targeted delivery and controlled release of 10 B compounds in BNCT. In the early 1990s, the application of liposomal boron delivery systems in BNCT was first investigated, and since then, numerous outstanding studies have been conducted on the use of liposomes in BNCT …”

Synthesis, characterization and radiolabeling of carborane-functionalized tetrazines for use in inverse electron demand Diels–Alder ligation reactions

“…Dicarba-closo-dodecaboranes are attractive synthons for developing inorganic pharmaceuticals [1][2][3][4][5][6][7][8], radiopharmaceuticals [9], fluorophores [10], and boron neutron capture therapy (BNCT) [11][12][13][14][15] or synovectomy (BNCS) agents [16,17]. Carboranes are biocompatible, resistant to enzymatic modification, and can be linked to or incorporated within a variety of different targeting vectors.…”