As an anti-metabolic drug, methotrexate (MTX) plays an important role in the treatment of various malignant tumors. However, several side effects such as low selectivity and high toxic of MTX limited its further applications. With aims to increase its accumulation in the tumor sites and reduce the toxicity of normal tissue nonspecific uptake, a self-assembled hyaluronic acid-alendronate-methotrexate nanoparticle (HA-ALN-MTX NPs) with a dual-tumor-targeted drug loaded system was designed and synthesized with an average particle size of 265.6 ± 13.3 nm. The advantage of this nanosystem is that the anticancer drug MTX can be used as a tumor-targeted ligand for folate acid receptors (FA), and hyaluronic acid (HA) can be used as another tumor targeted ligand for CD44 receptors. In vitro experiments confirmed that HA-ALN-MTX NPs has lower toxic effect on normal tissue cells HUVECs and has relatively high proliferation inhibition effect on tumor cells A549. Moreover, the inhibition effect could be adjusted by altering the dose of given drugs. All these results revealed that the prepared HA-ALN-MTX NPs could be selectively taken up by tumor cells by FA and CD44 receptor-mediated endocytosis. Therefore, self-assembled HA-ALN-MTX NPs targeted by these FA/CD44 receptors for anticancer drugs could act as effective antitumor drugs.
Keywords: Alendronate; Hyaluronic acid; Methotrexate; Nano-drug carrier; Nanoparticles.
Copyright © 2020. Published by Elsevier B.V.