In-vivo imaging of nanoshell extravasation from solid tumor vasculature by photoacoustic microscopy
In this study, high resolution reflection-mode (backward-mode) photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. This study takes advantage of the strong near-infrared absorption of nanoshells, a novel type of optically tunable gold nanoparticles that tend to extravasate from leaky tumor vasculatures (i.e., passive targeting) via the "enhanced permeability and retention" effect due to their nanoscale size. Tumors were grown in immunocompetent BALB/c mice by subcutaneous inoculation of CT26.wt murine colon carcinoma cells. PEGylated nanoshells with a peak optical absorption at ~800 nm were intravenously administered. Pre-scans prior to nanoshell injection were taken using a 584-nm laser source to highlight blood content and an 800-nm laser source to mark the background limit for nanoshell accumulation. After injection, the three-dimensional nanoshell distribution inside the tumor was monitored by PAM for 7 hours. Experimental results show that nanoshell accumulation is heterogeneous in tumors: more concentrated within the tumor cortex and largely absent from the tumor core. This correlates with others' observation that drug delivery within tumor cores is ineffective because of both high interstitial pressure and tendency to necrosis of tumor cores. Since nanoshells have been recently applied to thermal therapy for subcutaneous tumors, we anticipate that PAM will be important to this therapeutic technique.
Additional Information© 2007 Society of Photo-Optical Instrumentation Engineers (SPIE). We are grateful to Gina Lungu, Ovidiu Cracium, Kelly L. Gill for assistance with cell culture and veterinary procedure, and to Jung-Taek Oh, Hao F. Zhang, and Konstantin Maslov for technical advice and prior system development. This project is sponsored in part by the National Institutes of Health grants R01 EB000712 and R01 NS46214, and in part by the Advanced Technology Program at NIST, cooperative agreement #70NANB4H3040. Travel support from National Tsing Hua University, Taiwan is also greatly appreciated.
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