The synergistic effect of hyperthermia and chemotherapy in magnetite nanomedicine-based lung cancer treatment

Abstract

Background: Lung cancer is the leading cause of cancer patient death in the world. There are many treatment options for lung cancer, including surgery, radiation therapy, chemother-apy, targeted therapy, and combined therapy. Despite significant progress has been made in the diagnosis and treatment of lung cancer during the past few decades, the prognosis is still unsatisfactory. Purpose: To resolve the problem of chemotherapy failure, we developed a magnetite-based nanomedicine for chemotherapy acting synergistically with loco-regional hyperthermia. Methods: The targeting carrier consisted of a complex of superparamagnetic iron oxide (SPIO) and poly(sodium styrene sulfonate) (PSS) at the core and a layer-by-layer shell with cisplatin (CDDP), together with methotrexate – human serum albumin conjugate (MTX −HSA conjugate) for lung cancer-specific targeting, referred to hereafter as SPIO@PSS/ CDDP/HSA−MTX nanoparticles (NPs). Results: SPIO@PSS/CDDP/HSA−MTX NPs had good biocompatibility and stability in physiological solutions. Furthermore, SPIO@PSS/CDDP/HSA−MTX NPs exhibited a higher temperature increase rate than SPIO nanoparticles under irradiation by a radiofrequency (RF) generator. Therefore, SPIO@PSS/CDDP/HSA−MTX NPs could be used as a hyperthermia inducer under RF exposure after nanoparticles preferentially targeted and then accumulated at tumor sites. In addition, SPIO@PSS/CDDP/HSA−MTX NPs were developed to be used during combined chemotherapy and hyperthermia therapy, exhibiting a synergistic anticancer effect better than the effect of monotherapy. Conclusion: Both in vitro and in vivo results suggest that the designed SPIO@PSS/CDDP/ HSA−MTX NPs are a powerful candidate nanoplatform for future antitumor treatment strategies.