Development of zinc gallate based formulations for detection, targeted ¹⁰B delivery and prognosis in cancer treatment by boron neutron capture therapy

Cancer research is directed for non-invasive and multimodal utility for diagnosis and therapy as well as evaluation of treatment success to avoid recurrence of cancer and metastasis. Hence, we have developed biocompatible, tumor targeting nano formulations consisting of zinc gallate (ZnGa₂O₄:0.5%Cr) based persistent luminescence nanoparticles (PLNPs) loaded with ¹⁰B (OH)₃ and further conjugated with pH- (low)-insertion peptide (pHLIP) which has affinity for local acidity of cancerous cells. The formulations exhibited ability for detection of cancerous tissues and effective treatment by boron neutron capture therapy (BNCT) as well as facilitated in vivo bioimaging. The chemicals used for preparation of nano formulations viz., zinc nitrate, gallium nitrate, chromium nitrate and chemicals for functionalization like TEOS, CTAB, APTMS, HBTU, EDAC as well as amino acids for synthesis of peptide were procured from Sigma-Aldrich, India. The ZnGa₂O₄: (0.05%)Cr PLNPs were synthesized and characterized by powder XRD and TEM analyses. The PLNPs exhibited emission centered at 690 nm for ~24 h up on exposure to UV or LED. They were functionalized with silica and conjugated with ¹⁰B (OH)₃ and further with pHLIP to obtain the test formulations which were evaluated for cellular internalization and biocompatibility and against melanoma and fibrosarcoma induced in C57BL/6 and BALB/c mice, respectively. It was evaluated for therapeutic utility by i.v. injection of formulation followed by exposure of tumor region of mice with epithermal neutrons having an energy of 3 MeV and a flux of 2 × 10⁵ neutrons·cm^-2·s^-1 for 20 min and treatment repeated once after 2 days. The treatment was coupled with in vivo imaging and ex vivo studies on different organs of mice by photon imager. The treatment was followed by monitoring the tumor volume for next 15 days. Further, histopathological studies were performed on tissues of diverse organs and tumors. The evaluation of formulations against tumor in C57BL/6, BALB/c mice by BNCT revealed ~80-85% reduction in tumor volume after exposure to neutrons and monitored the treatment for 15 days. The histopathological studies indicated no signs of any damage to the vital organs for both control and treated mice proving non-toxicity of formulations and hence biocompatibility. The results have exhibited multimodal utility and potency of formulations, encouraging for their further evaluations anticipating their clinical use for BNCT assisted with bioimaging. (author)