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We have shown that high epithelial cell density is a major barrier to the distribution of nano-sized molecules in solid tumors, and tumor priming (expansion of interstitial space using an apoptosis-inducing pretreatment) can promote drug delivery. This study evaluated the optimal conditions of paclitaxel tumor priming (time window, particle size) and its effects on the delivery and efficacy of nanomedicines, in mice bearing human xenograft tumors. A single intravenous injection of paclitaxel induced apoptosis, expanded the interstitial space, vessel diameter and blood-perfused area, and promoted the delivery and interstitial dispersion of fluorescence-labeled latex beads (100 and 200 nm diameter, administered 48 hr after paclitaxel), in a tumor-selective manner. Paclitaxel tumor priming also enhanced the tumor delivery and antitumor activity of doxorubicin-loaded liposomes (85 nm) without affecting the delivery to noncancerous host tissues or enhancing host toxicity. Tumor priming represents a potentially useful means to promote tumor-selective delivery and efficacy of nanomedicines.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA