Development of self-powered multifunctional piezomagnetic nanoparticles for non-invasive post-surgical osteosarcoma theranogeneration

Non-invasive treatment approaches are gaining increased attention in recent times due to the potential improvement in treatment efficiency. Here we report a brand-new ultrasound (US), magnetic field (MF), and light responsive nanoparticle system based on piezoelectric barium titanate and superparamagnetic iron oxide nanoparticles termed as PiezoMagnetic nanoparticles (PMNPs) for the multimodal anticancer treatment, complimentary imaging, and non-invasive cell stimulation. Systematic electrical studies reveal that PMNPs exhibit superior ferroelectric and conducting properties and produce electrical signals analogous to native tissues when mechanically stimulated and using Food and Drug Administration (FDA) approved Low intensity Pulsed Ultrasound (LIPUS) non-invasively for cell stimulation. The green energy generation from PMNPs are further proved by the real-time demonstration of commercial LED lit-up. Thus, as a proof of concept, we have demonstrated a stepwise treatment efficacy of PMNPs for the post-surgical osteosarcoma therapy, diagnosis, and regeneration (termed as Theranogeneration). The PMNPs exhibited excellent anticancer properties to eradicate the residual osteosarcoma cells by magnetic hyperthermia, photothermal and photodynamic therapy along with complimentary imaging capabilities as X-ray computed tomography contrast agent and label free fluorescent probe. The conjugation of risedronate R (RIS)- a new generation bisphosphonates to PMNPs imparted bone seeking property to PMNPs. Therefore, as a result of noninvasive cell stimulation properties of PMNPs under LIPUS and LIPUS mediated RIS release from PMNPs resulted in enhanced bone regeneration and bone turnover which helps to repair the large bone defects occurs in osteosarcoma resection. Thus, the study corroborates the development of a potential bioactive piezoelectric nanoplatform that can be used to control the cell behaviour and fate in order to develop new types of therapies for multiple diseases including various types of cancers in remotely controlled approaches.