| Popis: |
Geraniol (GER), widely found in nature, exerts effective anti-tumoral activity against various malignant tumors. However, its low water solubility and poor bioavailability have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive GER hyaluronic acid (HA) polymer prodrug was synthesized by conjugating GER to HA using a disulfide bond. The synthesized prodrug (HSSG) as a molecular structural motif could self-assembly into simple yet multifunctional nanoparticles (HSSG NPs) in aqueous solution. The HSSG NPs displayed an average diameter of ∼110 nm with a uniformly spherical shape and maintained stability in different physiological media. Moreover, these NPs showed accelerated drug release rates when they were exposed to buffers that mimicked the multi-hallmarks in the tumor microenvironment (pH/glutathione/hyaluronidase). Furthermore, the results of fluorescent microscope and flow cytometry verified that the nanosystems were selectively uptaken by human hepatocellular carcinoma cell lines HepG2 and Huh7 via CD44 receptor-mediated internalization through the targeting. In addition, in the H22 tumor-bearing mice as the model, HSSG NPs could accumulate within tumor sites for a longer period. Notably, in vitro and in vivo antitumor results demonstrated that HSSG NPs significantly promoted the death of cancer cells and enhanced the inhibition of tumor growth while reducing the toxicity as compared to GER and HCCG NPs. Therefore, the HSSG NPs as the simple and efficient platform have great potential in tumor-targeting drug delivery and therapy. |
