Inhibitory Effect of Tanshinone IIA Nanomicelles on Tumor Growth and Angiogenesis in Mice with Cervical Carcinoma Transplantation

Abstract

In recent years, traditional Chinese medicine (TCM), represented by tanshinone (Tas) and ganoderan polysaccharides, has attracted the attention of many scientists due to its mild effect of inhibiting tumors. In this research, poly-gamma-glutamic acid (γ-PGA) was degraded into small molecule γ-PGA fragments by high-temperature acidolysis, and L-phenylalanine ethylester (L-PAE) was combined with small molecule γ-PGA fragments to generate γ-PGA-LA by dehydration condensation. The material was mixed with fat-soluble Tas IIA to form PL-Tas IIA nanomicelles (NMs). In addition to physical characterization, the in vitro biological activity of the material was detected to establish a tumor-bearing nude mouse model, which was inoculated with cervical cancer HeLa cells. The nude mouse models were grouped, and the effect of NMs on the growth of transplanted tumors was observed by intraperitoneal injection. The results revealed that the nanoparticle size was approximately 139.6±3.8 nm, and it had a good EPR effect, which was conducive to passive targeted therapy of tumors. The polydispersity coefficient and zeta potential were 0.138±0.005 and 33.6±1.6 mV, respectively. The NM was cocultured with the cells under various concentration conditions, and the cell survival rate was more than 85%. The tumor cell uptake performance of the NM was ideal, and the cell uptake ratio reached 71.62% at 60 min, as determined by flow cytometry. An in vivo tumor test demonstrated that PL-Tas IIA had a favorite tumor inhibition effect. The tumor-bearing nude mouse model showed that the prepared NMs can inhibit tumor growth, induce angiogenesis of xenografts, and further induce tumor cell apoptosis, further verifying that the prepared NMs can inhibit cervical cancer tumor growth.