摘要
Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells(MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles(NP)with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel(DTX) in NP, delivered via MSC accumulated in the lung. Both in vitro MSC/A549 cell experiments and in vivo MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. In vivo assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells(MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles(NP)with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel(DTX) in NP, delivered via MSC accumulated in the lung. Both in vitro MSC/A549 cell experiments and in vivo MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. In vivo assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.
基金
supported by grants from the Natural Science Foundation of China(Nos.81771966,31371404,31401187 and 31571429)
the Fundamental Research Funds for the Central Universities(Lin Mei,China)
the Guangdong Natural Science Funds for Distinguished Young Scholar(No.2014A030306036,China)
the Natural Science Foundation of Guangdong,China(2015A030311041,2015A030313763)
Science and Technology Planning Project of Guangdong Province,China(Nos.2016A020217001 and 2014A020212466)
the Shenzhen Science and Technology Innovation Committee(JCYJ20160301152300347,JCYJ20160531195129079,JCYJ20170412095722235,JCYJ2016042-9171931438,and GJHZ20150316160614842,China)
Guangdong Province Medical Science and Technology Research Fund(A2016445,China)