바로가기  >

Abstract
Tumor microenvironment is a significant physical barrier to the effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pretreated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. We hypothesize that timely priming at the early stage of primary tumors will help control metastasis. To test this, we primed orthotopic 4T1 breast tumors with a paclitaxel (PTX)-loaded iron-oxide-decorated poly(lactic- co-glycolic acid) nanoparticle (NP) composite (PTX@PINC), which can be quickly concentrated in target tissues with the aid of an external magnet, and monitored its effect on the delivery of subsequently administered NPs. Magnetic resonance imaging and optical whole-body imaging confirmed that PTX@PINC was efficiently delivered to tumors by the external magnet and help loosen the tumors to accommodate subsequently delivered NPs. Consistently, the primed tumors responded to Doxil better than nonprimed tumors. In addition, lung metastasis was significantly reduced in the animals PINC-primed prior to Doxil administration. These results support that PINC combined with magnetophoresis can facilitate the timely management of primary tumors with a favorable secondary effect on metastasis.

Author information

Park J1,2, Park J1, Castanares MA2, Collins DS2, Yeo Y1,3.
1
Department of Industrial and Physical Pharmacy , Purdue University , 575 Stadium Mall Drive , West Lafayette , Indiana 47907 , United States.
2
Lilly Research Laboratories, Lilly Corporate Center , Eli Lilly and Company , Indianapolis , Indiana 46285 , United States.
3
Weldon School of Biomedical Engineering , Purdue University , 206 South Martin Jischke Drive , West Lafayette , Indiana 47907 , United States.