Lymphatics drain nanoparticles from tumours – Nature Materials

Nanoparticle transport into and out of solid tumours is an important, translationally relevant phenomenon. Harnessing the characteristics of the remodelled tumour vasculature has led to improvements in clinical standards of care, namely by enabling clinically approved nanoparticle formulations against solid tumours (for example, protein-bound paclitaxel and lipid nanoparticles). In addition to blood vasculature remodelling, cancer also alters the functions of lymphatic vessels within tumours in a myriad of ways. In the context of systemically delivered nanomedicines, these changes have been widely hypothesized to increase the retention of nanoparticles within solid tumours. This is a puzzling assumption, given that lymph node metastasis is the most common and earliest form of metastasis, and sentinel lymph node mapping using colloidal contrast agents constitutes a routine part of standard clinical care used worldwide. Moreover, numerous studies have demonstrated that therapeutic nanoparticles drain from tumours to nearby lymph nodes, termed tumour-draining lymph nodes1,2,3,4,5. Now, writing in Nature Materials, Nguyen et al.6 report that nanoparticles exit tumours through lymphatic vessels within or around the tumour site, following two distinct mechanisms that are dependent on the nanoparticle size. These findings, together with previous knowledge about the active transcytosis entry pathway of nanoparticles into tumours7, provide a solid framework for engineering improved nanomaterials for cancer treatment and detection.