Non-interference delivery of Ce6 and DOX in NIR light-responsive liposomes for synergetic cervical cancer therapy
Jia Zhang, Yibo Yang, Yanting Gao, Zhimin Bai, Xin Zhang, Kun Li, Zhiwei Liu, Ming Shi, Yunwei Zhao, Jidong Wang, Jian Li
Abstract
Abstract Multi-model combination treatment of malignant tumors can make up for the shortcomings of single treatment through multi-target and multi-path to achieve more ideal tumor treatment effect. However, the mutual interference of different drugs in the delivery process in vivo and the difficulty of effective drug accumulation in tumor cells are the bottlenecks of combined therapy. To this project, light-responsive liposomes loading doxorubicin (DOX) and chlorin e6 (Ce6) (DOX-Ce6-Lip) without mutual interference were engineered by thin film hydration method. This kind of nano-drug delivery system increased the drugs concentration accumulated in tumor sites through enhanced permeability and retention effect, and reduced the toxic and side effects of drugs on normal tissues in vivo . In addition, after entering the tumor cells, Ce6 produced a large number of reactive oxygen species under 660 nm NIR laser irradiation, which further oxidized the unsaturated fatty acid chain in the liposomes and caused the collapse of the liposomes, thus realizing the stimulus-responsive release of Ce6 and DOX. The concentrations of DOX and Ce6 in the tumor cells rapidly reached the peak and achieved a more effective combination of chemotherapy and photodynamic therapy (PDT). Consequently, DOX-Ce6-Lip followed by 660 nm NIR irradiation achieved an efficient tumor growth inhibition of 71.90 ± 3.14%, indicating the versatile potential of chemotherapy and PDT. In conclusion, this study provides a delivery scheme for drugs with different solubilities and an effectively combined anti-tumor therapy method.