(-)-Epigallocatechin-3-gallate encapsulated realgar nanoparticles exhibit enhanced anticancer therapeutic efficacy against acute promyelocytic leukemia

Realgar and (-)-Epigallocatechin-3-gallate (EGCG) are natural medicines that inhibit cancer cell growth, resulting in inhibition of formation and development of tumors. The anticancer effects of realgar and EGCG were greatly improved following formulation as nanoparticles. EGCG has received increased attention as a drug carrier. The aim of this study was to prepare a new nanomedicine, (EGCG-RNPs), in which encapsulated nano-realgar. EGCG-RNPs were prepared by coprecipitation and characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), particle size and zeta potential, X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and <i>in vitro</i> release. Furthermore, we evaluated the antiproliferative effects of EGCG-RNPs on HL-60 cells in vitro, antitumor effect by intratumoral injection of EGCG-RNPs into solid tumors derived from APL HL-60 cells in vivo. Possible mechanisms were evaluated using uptake and efflux experiments in HL-60 cells. The results showed that the average particle size and zeta potentials of EGCG-RNPs was 200.3 ± 1.23 nm and −46.8 ± 1.31 mV. Controlled release of EGCG-RNPs was sustained and continued up to 72 h in vitro. Compared with nano-realgar and EGCG + RNPs (EGCG and nano-realgar physical mixing), EGCG-RNPs significantly inhibited growth of HL-60 cells. In a solid tumor model, EGCG-RNPs decreased tumor volumes, with an inhibitory rate of 60.18% at a dose of 70 mg · kg⁻¹. The mechanisms of antitumor improvement may correlate with the increased uptake of realgar and prolonged the retention time of realgar in HL-60 cells due to EGCG as a carrier. EGCG-RNPs could enhance anticancer therapeutic efficacy for acute promyelocytic leukemia.

雄黄与表没食子儿茶素没食子酸酯((-)-Epigallocatechin-3-gallate, EGCG)均为可抑制癌细胞增殖、阻滞肿瘤形成与发展的天然药物。将二者制备为纳米制剂后，其抗癌活性可得到显著提升。其中，EGCG作为药物载体受到了越来越多的关注。本研究旨在制备一种新型纳米药物EGCG-RNPs，该制剂包载纳米雄黄。本研究采用共沉淀法制备EGCG-RNPs，并通过透射电子显微镜（TEM）、差示扫描量热法（DSC）、粒径与Zeta电位检测、X射线衍射、傅里叶变换红外光谱（FTIR）以及体外（in vitro）释放实验对其进行表征。此外，本研究还体外评估了EGCG-RNPs对HL-60细胞的抗增殖活性，通过瘤内注射给药的方式，在急性早幼粒细胞白血病（APL）HL-60细胞来源的实体瘤模型中评价了其体内抗肿瘤效果。通过在HL-60细胞中开展摄取与外排实验，探讨了其可能的作用机制。结果显示，EGCG-RNPs的平均粒径与Zeta电位分别为200.3±1.23 nm与-46.8±1.31 mV。EGCG-RNPs在体外可实现持续的控释效果，释药过程可维持至72小时。与单独的纳米雄黄以及EGCG与纳米雄黄物理混合的制剂（EGCG+RNPs）相比，EGCG-RNPs可显著抑制HL-60细胞的增殖。在实体瘤模型中，EGCG-RNPs可减小肿瘤体积，在70 mg·kg⁻¹的给药剂量下，肿瘤抑制率可达60.18%。其抗肿瘤活性增强的机制可能与EGCG作为载体提升了雄黄的细胞摄取效率、延长了雄黄在HL-60细胞内的滞留时间相关。综上，EGCG-RNPs可增强急性早幼粒细胞白血病的抗癌治疗效果。