面向抗肿瘤的可协同光热/化疗纳米体系的构建及其药物控释行为

Construction of a synergistic photothermic/chemotherapeutic nanosystem for antitumor and study of its drug controlled release behavior

传统治疗肿瘤的方式包括手术、放疗和化疗。手术治疗创伤大、易复发,放疗周期过长,尽管化疗被认为是消灭肿瘤细胞的首选但其存在着明显的毒副作用,长期化疗会严重影响患者的生存质量。因而,设计一种响应型功能载体实现抗肿瘤药物的高效运输及协同抑瘤在临床上具有广阔的前景。本文以CuS为光热剂,采用溶剂热及去模板法在CuS表面包被上介孔二氧化硅(mSiO_(2)),借助mSiO_(2)的大比表面积制备出高负载盐酸阿霉素(DOX)的纳米药物体系CuS@mSiO_(2)-DOX。XRD、UV-vis、SEM、TEM及DLS结果证实成功的合成了颗粒尺寸约为300~400 nm的CuS@mSiO_(2)-DOX纳米体系,且DOX的负载效率可高达99.76%。CuS@mSiO_(2)-DOX在pH=5.5、45℃的条件下24 h时药物释放率达到63.44%,相比正常生理环境(pH=7.4、35℃)释放率提高了近20倍,呈现出明显的pH及温度响应释放特性。对纳米载药体系CuS@mSiO_(2)的光热性能及体外细胞毒性进行了测试,结果显示CuS@mSiO_(2)表现出良好的光热稳定性、光热转换效率达到31.67%,且对正常的人肝细胞(HL-7702)呈低毒性。CuS@mSiO_(2)纳米体系具有较好的生物相容性、良好的光热转换及载药性能,吸附DOX后体系表现出优异的pH及激光响应型药物控释性能,在联合光热-化疗协同抗肿瘤领域有望得到广泛应用。

Traditional methods of cancer treatment include surgery,radiotherapy,and chemotherapy.The surgical treatment is highly traumatic and easy to recur,while the period of radiotherapy is too long.Although chemotherapy is considered as the first choice to destroy tumor cells,it has obvious toxic and side effects,and the longterm chemotherapy can seriously affect the quality of the patients'life.In this study,CuS was selected as a photothermal agent,and mesoporous silica(mSiO_(2))was coated on the surface of CuS using the solvothermal and template removal methods.With the aid of the large specific surface area of mSiO_(2),a highly doxorubicin hydrochloride(DOX)loaded nanodrug system was prepared(CuS@mSiO_(2)-DOX).XRD,UV-vis,SEM,TEM,and DLS results jointly confirm that the CuS@mSiO_(2)-DOX nanosystem with a particle size of approximately 300-400 nm is successfully synthesized,and the loading efficiency of DOX in this system can reach up to 99.76%.The 24 h-drug release rate of CuS@mSiO_(2)-DOX reaches 63.44% under the conditions of pH=5.5 and 45℃,which is nearly 20 times higher than that under the normal physiological environment(pH=7.4 and 35℃),indicating that the CuS@mSiO_(2)-DOX nanosystem possesses obvious pH and temperature responsive release characteristics.In addition,the photothermal performance and in-vitro cytotoxicity of the CuS@mSiO_(2) nanodrug delivery system was tested,and the results show that CuS@mSiO_(2) exhibits a good photothermal stability with a photothermal conversion efficiency of 31.67%,and which also reveals low toxicity to normal human liver cells(HL-7702).CuS@mSiO_(2) nanosystem has good biocompatibility,outstanding photothermal conversion and drug loading properties,and after DOX adsorption,the system exhibits excellent pH and laser responsive drug controlled release performance,which is expected to be widely used in the field of combining the photothermal-chemotherapy to synergistically resist tumor.