Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect.
Abdul Basith FithroniKazuko KobayashiHirotaka UjiManabu IshimotoMasaru AkehiTakashi OhtsukiEiji MatsuuraPublished in: Cells (2022)
BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers ( o- , m- , and p- carborane) and three related alkylated derivatives, i.e., 1,2-dimethy- o- carborane (diC1-Carb), 1,2-dihexyl- o- carborane (diC6-Carb), and 1,2-didodecyl- o- carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT.
Keyphrases
- cancer therapy
- drug delivery
- cell death
- papillary thyroid
- wound healing
- cell cycle arrest
- induced apoptosis
- squamous cell
- squamous cell carcinoma
- computed tomography
- type diabetes
- single molecule
- metabolic syndrome
- lymph node metastasis
- pet imaging
- ionic liquid
- young adults
- childhood cancer
- ultrasound guided
- insulin resistance
- drug induced
- endoplasmic reticulum stress
- case control