Sun Hui-Ping, Su Jing-Han, Meng Qing-Shuo, Yin Qi, Zhang Zhi-Wen, Yu Hai-Jun, Zhang Peng-Cheng, Wang Si-Ling, Li Ya-Ping
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Acta Pharmacol Sin. 2016 Jul;37(7):941-9. doi: 10.1038/aps.2016.20. Epub 2016 May 2.
To improve the therapeutic efficacy of cancer treatments, combinational therapies based on nanosized drug delivery system (NDDS) has been developed recently. In this study we designed a new NDDS loaded with an anti-metastatic drug silibinin and a photothermal agent indocyanine green (ICG), and investigated its effects on the growth and metastasis of breast cancer cells in vitro.
Silibinin and ICG were self-assembled into PCL lipid nanoparticles (SIPNs). Their physical characteristics including the particle size, zeta potential, morphology and in vitro drug release were examined. 4T1 mammalian breast cancer cells were used to evaluate their cellular internalization, cytotoxicity, and their influences on wound healing, in vitro cell migration and invasion.
SIPNs showed a well-defined spherical shape with averaged size of 126.3±0.4 nm and zeta potential of -10.3±0.2 mV. NIR laser irradiation substantially increased the in vitro release of silibinin from the SIPNs (58.3% at the first 8 h, and 97.8% for the total release). Furthermore, NIR laser irradiation markedly increased the uptake of SIPNs into 4T1 cells. Under the NIR laser irradiation, both SIPNs and IPNs (PCL lipid nanoparticles loaded with ICG alone) caused dose-dependent ablation of 4T1 cells. The wound healing, migration and invasion experiments showed that SIPNs exposed to NIR laser irradiation exhibited dramatic in vitro anti-metastasis effects.
SIPNs show temperature-sensitive drug release following NIR laser irradiation, which can inhibit the growth and metastasis of breast cancer cells in vitro.
为提高癌症治疗的疗效,基于纳米药物递送系统(NDDS)的联合疗法近来已被开发。在本研究中,我们设计了一种负载抗转移药物水飞蓟宾和光热剂吲哚菁绿(ICG)的新型NDDS,并研究了其对体外乳腺癌细胞生长和转移的影响。
水飞蓟宾和ICG自组装成聚己内酯脂质纳米颗粒(SIPNs)。检测了它们的物理特性,包括粒径、zeta电位、形态和体外药物释放。使用4T1哺乳动物乳腺癌细胞评估其细胞摄取、细胞毒性以及对伤口愈合、体外细胞迁移和侵袭的影响。
SIPNs呈现出形状明确的球形,平均粒径为126.3±0.4 nm,zeta电位为-10.3±0.2 mV。近红外激光照射显著增加了水飞蓟宾从SIPNs中的体外释放(前8小时释放58.3%,总释放量为97.8%)。此外,近红外激光照射显著增加了SIPNs对4T1细胞的摄取。在近红外激光照射下,SIPNs和IPNs(仅负载ICG的聚己内酯脂质纳米颗粒)均导致4T1细胞的剂量依赖性消融。伤口愈合、迁移和侵袭实验表明,经近红外激光照射的SIPNs表现出显著的体外抗转移作用。
SIPNs在近红外激光照射后呈现温度敏感型药物释放,可在体外抑制乳腺癌细胞的生长和转移。