Respiratory pulmonary infections are a serious threat to human health. Their therapy is primarily based on the use of antibiotics. However, non-specific accumulation and low concentration in the target tissue reduce therapeutic effectiveness, cause side effects, and promote the development of antibiotic resistance. In this study, metal-organic frameworks (MOFs) with MIL-101 (Cr) structure were used for delivery of rifampicin to the lungs. The nanoparticles showed high antibiotic loading by mass, namely (127 ± 8) % for MIL-101 (Cr) and (82 ± 7) % for amino-modified NH2-MIL-101 (Cr). The kinetics of drug release had rapid and prolonged phases with up to 40 % of the loaded drug released in 7 h. It induces a significant inhibition of bacterial viability at a concentration of nanoparticles as low as 1 mg/L. After intravenous administration, the particles showed high tropism for lung accumulation reaching concentration of almost 300 %/g of tissue, more than 10 times higher than concentrations in other tissues. This study demonstrates the effectiveness of using MIL-101 (Cr) MOFs for pulmonary drug delivery and holds significant promise for developing antibacterial therapies.
Breast cancer remains one of the most common malignancies worldwide. Highly invasive HER2-positive breast cancer carries a high risk of metastasis and poses a significant therapeutic challenge. Boron neutron capture therapy (BNCT) may be an option for patients with this severe diagnosis. Here we evaluated the effectiveness of BNCT with elemental boron nanoparticles obtained by laser fragmentation and coated Silane-PEG-COOH and conjugated with the Affibody ZHER2:342 guide protein (BPs) against the HER2-positive breast cancer. The MTT assay after BNCT with BPs revealed an almost twofold reduction in surviving BT-474 tumor cells compared to the control group. The results of the clonogenic test showed totally death of BT-474 cells after BNCT with BPs at a concentration of 40 μg/mL in the culture medium. The same results was found for in vivo. In female SCID mice bearing BT-474 breast tumor xenografts, BNCT with intratumoral injection of BPs at a dose of 60 mg/kg led to a significant slowdown in xenograft growth beginning on the 17th day compared with control animals and the 39th day compared with irradiated females. A single intratumoral administration of BPs at a dose of 60 mg/kg did not show toxic effects. Histological examinations did not reveal systemic accumulation of the studied BPs in major organs; instead BPs was selectively retained within the xenografts and surrounding tissues. Thus, laser fragmented functionalized with Silane-PEG-COOH and the Affibody ZHER2:342 (BPs B-PEG-AFF) represent a promising platform for boron delivery in targeted BNCT applications.