Journal
MOLECULAR PHARMACEUTICS
Volume 6, Issue 5, Pages 1343-1352Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp900022m
Keywords
Worm micelle; optical imaging; in vivo tracking; tumor; paclitaxel; near infrared; drug delivery; block copolymer
Funding
- NCRR NIH HHS [S10 RR022575, S10 RR022575-01A1] Funding Source: Medline
- NHLBI NIH HHS [R01 HL062352-09A1, R01 HL062352] Funding Source: Medline
- NIAMS NIH HHS [R21 AR056128-02, R21 AR056128, R21 AR056128-01A1] Funding Source: Medline
- NIBIB NIH HHS [R01 EB007049-01, R01 EB007049, R01 EB007049-02, R01 EB007049-03] Funding Source: Medline
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Shape effects of synthetic carriers are largely unexplored in vivo, although recent findings suggest that flexible filaments can persist in the circulation even if microns in length. Here, to better assess biodistribution, a near-infrared fluorophore (NIRF) was incorporated into such block copolymer filomicelles, and both in vivo and ex vivo imaging show that the majority of these wormlike micelles remain in the circulation for at least a day after intravenous injection. NIRF imaging further suggests that filomicelles convect into a tumor and some fragments can penetrate into the tumor stroma. To assess a functional effect, the hydrophobic drug paclitaxel (tax) was loaded into both filomicelles and sonication-generated spherical micelles of the same copolymer. Intravenous injection of tax-loaded filomicelles nearly doubles the maximum tolerated dose of tax in normal mice compared to tax-loaded spherical micelles. In tumor-bearing mice, the higher dose of tax produces greater and more sustained tumor shrinkage and tumor cell apoptosis. These results thus begin to address mechanisms for how nonspherical carriers deliver both imaging agents and anticancer therapeutics to solid tumors.
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