Co-delivery of calreticulin DNA and doxorubicin by mPEG-LPEI-PCL micelle to exert synergistic anticancer effects through enhancing immunogenicity of cancer cells
Combination of chemotherapy with gene therapy is a promising strategy for cancer treatment.The aim of the current study is to simultaneously deliver the chemotherapeutic drug and gene (DNA) to the same tumor cell for better anti-tumor ability.We constructed an innovative cationic polymer poly (ethylene glycol)-g-linerpoly(ethyleneimine)-g-poly(ε-caprolactone) (mPEG-LPEI-PCL, PLP) as gene/drug co-delivery carrier.This PLP polymer could encapsulate drug and condense DNA simultaneously into a suitable size particle, with possible low cytotoxicity, high gene transfection efficiency and sustained drug release ability.In the current study, pcDNA3.1/ calreticulin (CRT) recombinant plasmid and chemotherapy drug Doxorubicin (DOX) were encapsulated into this novel PLP polymer simultaneously.Our results showed that the systemic administration of pcDNA-CRT plus DOX polymer induced a significant tumor suppression of mouse melanoma transplanted with B16F10 cells.We further demonstrated that the activation of tumor immune response of the mice was a result of overexpression of CRT protein, which was transfected by pcDNA3.1/CRT recombinant plasmid and further induced by co delivered of DOX.Then a synergistic enhancement of tumor immunity was triggered, resulting in more macrophages infiltration in tumor tissue and enhance tumor cell phagocytosis.Our results suggested that this novel multifunctional PLP is a promising carrier for the delivery of both gene and chemotherapeutic drugs together to achieve a synergistic antitumor effect.
mPEG-LPEI-PCL doxorubicin calreticulin tumor immunity co-delivery synergistic effect
Jing Wang Yong Yang Shao ping Yin Jie Mao Jing an Yang Jing jing Duan Wei Tian Xian jing Li Kai yong Hu Juan Li
State Key Laboratory of Natural Medicines, Department of Pharmaceutics and Research, Institute of Ph State Key Laboratory of Natural Medicines, Center for New Drug Safety Evaluation and Research, Insti
国内会议
江苏省药理学会青年工作委员会成立大会暨药理学科青年科技创新学术研讨会
苏州
英文
138-152
2013-05-24（万方平台首次上网日期，不代表论文的发表时间）