(512e) Optimizing the Delivery of Nano-Medicine in Tumors: Implications for Tumor Normalization

Recent advances in nanotechnology have offered a fresh hope for cancer detection, prevention, and treatment. Nanoparticles have the potential to incorporate multiple therapeutic, diagnostic and transport-facilitating agents. However, increased sophistication may necessitate increased size, which hinders delivery. Antiangiogenic cancer treatment can normalize the vasculature of a malignant tumor and enhance the delivery of the therapeutic agent [1, 2].

In this study we employed tracer-clearance experiments and high resolution 3-D images of normal and tumor vasculature [3]. Based on these images, we performed diffusion (random-walk) simulations of nanoparticles in the interstitial space of the tissue and calculated the time required for the particles to reach the vessel walls. The random-walk simulations confirmed the behavior that we observed in our clearance experiments. We also identified characteristic time scales that differ between normal and tumor tissue. Subsequently, on each of the 3-D images we were able to relate the characteristic time scales to simple, newly identified, measures of the vascular geometry that may be selectively targeted with antiangiogenic treatment to optimize delivery.

1. R. K. Jain, ?Normalizing Tumor Vasculature with Antiangiogenic Therapy: A new Paradigm for Combination Therapy,? Nature Medicine, 7(9), pp. 987-989, 2001.

2. R. K. Jain, ?Normalization of Tumor Vasculature: An emerging Concept in Antiangiogenic Therapy,? Science, 307 (58), pp. 58-62, 2005.

3. V. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, B. E. Bouma, ?Three-Dimensional Microscopy of vascular networks, lymphatics, cell viability and tissue microenvironment in vivo using frequency domain imaging,? accepted in Nature Medicine, 2009.