Imaging of lung metastases using CT-detectable microcapsules and their radiotherapeutic treatment using targeted carboplatin nanoparticles

Abstract

We aimed to image and treat the lung metastases of MM48 breast cancer cells in C3He/N mice by using microcapsules that release liposome-protamine-hyaluronic acid nanoparticles (LPH-NP) in response to two radiation sessions. In session one, computed tomography (CT)-detectable microcapsules containing P-selectin and 5% iopamiron were mixed with a 1 mL solution of 4% alginate, 3% hyaluronate, 1 mg ascorbate, and 1 μg/mL P-selectin. This was sprayed into 0.5 mmol/L FeCl2 containing 1 μg/mL VEGFR-1/2 antibodies (Abs). The mice were intravenously injected with microcapsules, which released the P-selectin, and then a CT study was performed to detect lung metastases. After the CT evaluation, the mice received 10 or 20 Gy (140 keV) of X-ray radiation to the lungs. In session two, carboplatin-LPH-NP was released into the tumor, which was treated with another dose of radiation. To do this, carboplatin LPH-NP was mixed with the cocktail used in session one and sprayed into 0.5 mmol/L FeCl2 containing 1 μg/mL anti-P-selectin Abs. Microcapsules (1 × 1010) were injected intravenously and then interacted with the P-selectin. The released carboplatin LPH-NP attacked lung metastases synergistically with radiation, which resulted in further reduction of the lung metastases.