温敏聚合物/纳米CuS复合微球在肿瘤光热化学联合治疗中的应用

Photothermal Therapy of Temperature-sensitive Polymer/CuS Nanoparticles Composite Microspheres in Cancer

利用湿化学法合成了具有光热效应的纳米硫化铜(Cu S)颗粒,采用沉淀聚合法,以N-异丙基丙烯酰胺(NIPAAm)和N-乙烯基吡咯烷酮(NVP)为共聚单体,锂藻土(laponite)作为交联剂,吸附纳米硫化铜,制备出兼具光热效应和温敏响应性的复合微凝胶[P(NIPAAm-co-NVP)/Cu S](NNC/Cu S),并测试其载药和药物缓释性能.实验结果表明,制备的纳米Cu S和NNC/Cu S复合微凝胶均在近红外区有很宽的光谱吸收带,在980 nm(0.51 W/cm2)激光的辐照条件下,NNC/Cu S复合微凝胶具有良好的光热效应,温度在8 min内可以升至51.9℃,对于Hela细胞杀伤效果明显,并随着激光照射时间的延长效果越好.复合微凝胶的载药量为0.15mg/mg,在p H=5.5的PBS缓冲液中累积药物释放为75%,高于p H=7.4的63%.同时光热效应对于温敏性载药微球的药物释放具有有效地调控作用,在药物释放阶段,激光照射段药物释放率明显高于未加激光照射段.另外聚合物与纳米Cu S的复合改善了纳米Cu S对于细胞的毒性,NNC/Cu S复合微凝胶细胞存活率为90.9%高于纳米Cu S的63%.

The copper sulfide（ Cu S） nano-particles which have the photothermal effect were prepared by wetchemical method. The polymer gel / copper sulfide [P（ NIPAAm-co-NVP） / Cu S ]（ NNC / Cu S） composite microspheres which possess both temperature sensitivity and photothermal effect were synthesized,using Nisopropylacrylamide（ NIPAAm） and N-Vinylpyrrolidone（ NVP） as monomers,laponite as crosslinking agents,then Cu S nanoparticles were adsorbed. Drug delivery performance and drug controlled release properties were also studied. The results showed that both Cu S nanoparticles and composite microspheres had a very wide spectral absorption band in the near infrared region. In the 980 nm（ 0. 5 W / cm^2） laser irradiation case,NNC /Cu S composite microspheres exhibit a good photothermal effect,the temperature of composite microspheres can raise to 51. 9 ℃ in 8 min. It can effetively kill Hela cell,the killing effect getting better with the increase of irradiation time. The drug loading is 0. 15 mg / mg,the cumulative drug release rate is 75% at p H = 5. 5 PBS buffer and 63% at p H = 7. 4. The photothermal effect can also effectively regulate drug release from temperature sensitive drug loaded microspheres. In drug release phase,the drug release rate was much improved when treated with 980 nm laser irradiation. On the other hand,the cell toxicity of NNC / Cu S composite microspheres was notably decreased. The cell viability of the composite microspheres was 90. 9%compared with 63% of Cu S nanoparticles.