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Oleic acid (OA) is a kind of monounsaturated omega-3 fatty acid that abounds in plants and animals which can induce apoptosis and has broad-spectrum inhibitory activity against a variety of tumor cell lines. However, OA is quite insoluble and thus inconvenient to be efficiently delivered in vivo. In this work, OA was fabricated into nanoparticles to generate OA elastic nanoparticles (OA-ENPs) with a particle size of 185.6 nm and good stability in various physiological media. OA-ENPs alone achieved a high tumor inhibition rate of 60.3% without significant side effect. More surprisingly, the resultant OA-ENPs displayed dose-dependent tumor targetability. Low dose of OA-ENPs (10 mg/kg) mainly distributed in the liver after intravenous injection, while high dose of OA-ENPs mainly distributed in tumor. At the high dose of 90 mg/kg, OA-ENPs accumulation in tumor reached nearly twice as that in the liver. Here we provide a simple but effective way to achieve excellent tumor targetability without the need of any surface modification of nanoparticles.

Hydroxy genkwanin (HGK), a flavonoid compound from natural resources, showed good inhibition against the growth of breast tumor cells. However, the poor solubility restricted the further study and the in vivo drug delivery of HGK. We prepared HGK nanosuspensions by antisolvent precipitation method and investigated their characterization, stability, hemolysis probability, release behavior in vitro, antitumor activity in vitro and in vivo, and preliminary safety through acute toxicity experiments. The resultant HGK nanosuspensions (HGK-NSps) showed an average diameter of (261.1 ± 4.8 nm), a narrow particle size distribution (PDI of 0.12 ± 0.01), spherical morphology, high drug-loading content (39.9 ± 2.3%, w/w), and good stability in various physiological media. HGK-NSps was safe for intravenous injection at low concentration and HGK was slowly released from the obtained nanosuspensions. HGK-NSps showed stronger cytotoxicity than free HGK against many tumor cells in vitro. Especially against MCF-7 cells, the IC50 value was decreased to 1.0 μg/mL, 5-fold lower than the HGK solution. In the in vivo antitumor activity study HGK-NSps (40 mg/kg) displayed a similar therapeutic effect to that of the paclitaxel injection (8 mg/kg). The preliminary acute toxicity test showed that even at the highest dose of 360 mg/kg (iv), HGK-NSps had 100% of mice survival and all the mice were in a good state, suggesting a maximum tolerated dose more than 360 mg/kg. The effective antitumor effect and good tolerance showed HGK-NSps were likely to become a safe and effective antitumor drug for the treatment of breast cancer in the future.

Due to their various biological activities that are beneficial to human health and antitumor effect, flavonoid compounds have attracted much attention in recent years. Hydrous icaritin (HICT) was such a flavonoid that can inhibit the growth of breast cancer and cancer stem cells. In order to overcome the insolubility problem, HICT was fabricated into nanorods (NRs) through anti-solvent precipitation in this paper using D-α tocopherol acid polyethylene glycol succinate and sodium oleate as a co-stabilizer meanwhile using the mixture of ethanol and acetone (1:2, v/v) as the organic solvent. The obtained HICT NRs showed an average particle size 222.0 nm with a small polydispersity index value of 0.124 and a high zeta potential of – 49.5 mV. HICT NRs could maintain similar particle size in various physiological medium and could be directly lyophilized without the addition of any cytoprotectants and then reconstituted into a colloidal system of similar size. The resultant HICT NRs had a high drug loading content of 55.6% and released HICT in a steady and constant pattern. MTT assay indicated NRs enhanced HICT’s antitumor activity to ninefold against MCF-7 breast carcinoma cells. In vivo studies demonstrated oral administration free HICT had almost no tumor inhibitory effect while HICT NRs showed a tumor inhibition rate of 47.8%. When intravenously injected, HICT NRs displayed similar therapeutic efficacy to paclitaxel injections (70.4% vs. 74.5%, TIR). This may be partly due to the high accumulation of the injected HICT NRs in tumor ranking only second to that in the liver but much higher than in other organs. These results demonstrated that HICT NRs could be a promising antitumor agent for the treatment of breast cancer in clinic.