High-frequency ultrasound-assisted drug delivery of chia, cress, and flax conjugated hematite iron oxide nanoparticle for sono-photodynamic lung cancer treatment in vitro and in vivo

Sono-photodynamic therapy (SPDT), which combines photodynamic (PDT) and sonodynamic (SDT) therapies with sensitizers, offers new avenues for cancer treatment. Even though new sensitizers for SPDT have been synthesized with great success, few of them are effectively used. The limited tumor-targeting specificity, inability to transport the sensitizers deeply intratumorally, and the deteriorating tumor microenvironment limit their anti-tumor effectiveness. The current study was carried out aiming at high-frequency ultrasound-assisted drug delivery of chia, cress and flax conjugated hematite iron oxide nanoparticles (CCF–HIONP) for photothermal–photodynamic lung cancer (LCA) treatment in vitro and in vivo as activated cancer treatment up-to-date modality. The study was conducted in vitro on human LCA cells (A-549) and the study protocol application groups in vivo on Swiss albino mice treated with benzo[a]pyrene only and were not received any treatment for inducing LCA, and only after LCA induction the study treatment protocol began, treatment was daily with CCF–HIONP as HIFU–SPDT sensitizer with or without exposure to laser (IRL) or high-frequency ultrasound (HIFU–US) or a combination of laser and/or high-frequency ultrasound for 3 min for 2 weeks. Revealed that HIONP can be employed as effective CCF delivery system that directly targets LCA cells. In addition, CCF–HIONP is a promising HIFU–SPS for HIFU–SPDT and when combined with HIFU–SPDT can be very effective in treatment of LCA–A549 in vitro (cell viability decreased in a dose-dependent basis, the cell cycle progression in G0/G1 was slowed down, and cell death was induced as evidenced by an increase in the population of Pre-G cells, an increase in early and late apoptosis and necrosis, and an increase in autophagic cell death) and benzo[a]pyrene LCA-induce mice in vivo (decreased oxidative stress (MDA), and ameliorated enzymatic and non-enzymatic antioxidants (SOD, GR, GPx, GST, CAT, GSH, and TAC) as well as renal (urea, creatinine) and hepatic (ALT, AST) functions, induced antiproliferative genes (caspase 3,9, p53, Bax, TNFalpha), suppressed antiapoptotic and antiangiogenic genes (Bcl2,VEGF respectively) and effectively reducing the growth of tumors and even leading to cancer cell death. This process could be attributed to photochemical and/or high-frequency sono-chemical activation mechanism HIFU–SPDT. The results indicate that CCF–HIONP has great promise as an innovative, effective delivery system for selective localized treatment of lung cancer that is activated by HIFU–SPDT.