Development of theranostic nanoparticles with the ability to break extracellular cellular matrix for enhanced nanoparticle delivery

X. Guo, W. Qian, A. Wang, L. Yang
Emory University, US

Keywords: breast cancer, nanoparticle, protease, drug delivery

Summary:

One of the major challenges in cancer treatment is low drug delivery efficiency. Although tumor targeted nanoparticles offer means to deliver imaging and therapeutic nanoparticles into the tumor cells, the presence of extensive tumor stroma in many human tumors creates a physical barrier that limits intra-tumor distribution of the nanoparticles. To facilitate movement and distribution of the nanoparticles, we produced nanoparticles conjugated with two extracellular matrix proteases, collagenase and/or hyaluronidase. These proteases can temporarily break down extracellular matrix and open microscopic channels, allowing nanoparticles to spread in the tumor. The objective of this study is to determine whether protease-conjugated nanoparticles have enhanced intra-tumor delivery. We found that proteases can be efficiently conjugated on the polymer-coated quantum dots. After incubation with 4T1 mammary breast cancer cell line, such nanoparticles are able to bind to the cells with intensive binding in the invasive edge of tumor cell clones. The collagenase shows even better effects than the hyaluronidase. Currently, we are working to improve the delivery efficiency and anti-tumor effect of nanoparticles carrying chemotherapy drugs, without or with being conjugated with targeting ligands, in an orthotopic mouse xenograft model with breast cancers.