酸响应聚合物-铂共轭纳米颗粒给药载体的抑癌作用

Tumor Inhibition of Acid-Responsive Polymer-Cisplatin Conjugate Nanoparticles Drug Delivery System

目的合成酸响应聚合物-铂共轭的纳米体系,验证该结合体作为给药载体对癌症细胞的抑制作用。方法合成酸响应聚合物-铂共轭的纳米药物载体,在酸性环境中模拟药物的释放,用噻唑蓝(MTT)法检测其对细胞活性的影响。结果聚合物-铂共轭纳米颗粒显示出可控的铂负载率,良好的酸响应药物释放动力学,在pH=7.4时,释放量很少,而在pH=5.0或6.0时药物释放明显。与游离顺铂相比,对于卵巢癌细胞显示出较高的体外细胞毒性,包裹在聚合物-铂共轭纳米颗粒中相当于7μmol·L-1游离顺铂的药物量,可以达到与50μmol·L-1游离顺铂药物相当的细胞毒性效果。结论聚合物-铂共轭纳米颗粒体系为酸响应药物输送体系,可以显著提高药物的生物利用度,有望在癌细胞内快速释放高剂量的化疗药物对癌细胞起到抑制作用,改善负载药物的治疗效果。

Objective To synthesize polymer-cisplatin conjugate nanoparticles for acid-responsive drug delivery, and verify the inhibitory effect of the nano-system on cancer cells. Methods Acid-responsive polymer-cisplatin conjugate nano-drug carrier was synthesized to simulate the drug release under an acidic environment. Cell viability was examined by MTT assay. Results The polymer-cisplatin nanoparticles exhibited well-controlled cisplatin loading rate, and excellent acid-responsive drug release kinetics. At pH 7. 4, little drug was released. At pH 5. 0 or 6. 0,the drug release was significant. Compared with free cisplatin,cisplatin in the conjugate nanoparticles showed higher cytotoxicity against ovarian cancer cells in vitro. An equivalent dose of 7 μmol·L^-1 cisplatin loaded in the conjugate nanoparticles exhibited same cytotoxicity as 50μmol·L^-1 free cisplatin.Conclusion Polymer-cisplatin conjugate is an acid-responsive drug delivery system that greatly improves the bioavailability of cisplatin to tumor cells. It is expected to play a better tumor inhibition effect by quickly releasing a high dose of chemotherapy drug inside tumor cells.