Normalization of Tumour Blood Vessels Improves the Delivery of Nanomedicines in a Size-Dependent Manner
Vikash P. Chauhan, Triantafyllos Stylianopoulos, John D. Martin, Zoran Popović, Ou Chen, Walid S. Kamoun, Moungi G. Bawendi, Dai Fukumura, Rakesh K. Jain
Abstract
Unfortunately, the increased hydrodynamic and steric hindrance resulting from the smaller vessel pores caused by normalization may compromise the advantage gained from enhanced convection. The blood vessels of cancerous tumours are leaky and poorly organized. Elevated tumour interstitial fluid pressure hinders drug delivery by abolishing the fluid pressure gradients that lead to rapid convective penetration into tumours. Orthotopic mammary tumour models were prepared by implanting a small piece of viable tumour tissue from a source tumour animal into severe combined immunodeficient mice bearing mammary fat pad chambers. The primary tumours were then measured every three days, beginning on day 0, using calipers. Tumour growth was quantified using the time for each to reach double its initial volume. The calculation was made as an average over the entire imaged volume for each tumour. Antiangiogenic therapies can repair tumour vessel abnormalities such as the large heterogeneous pores that facilitate leakiness by inducing vessel maturation.