The present studies noninvasively investigate the passive
tumor distribution potential of a series of poly(
ethylene glycol) (PEG) nanocarriers using a SkinSkan spectrofluorometer and an In Vivo Imaging System (IVIS) 100.
Fluorescein conjugated PEG nanocarriers of varying molecular weights (10, 20, 30, 40, and 60 kDa) were prepared and characterized. The nanocarriers were administered intravenously to female balb/c mice bearing subcutaneous 4T1
tumors. Passive distribution was measured in vivo (λ(exc), 480 nm; λ(em), 515-520 nm) from the
tumor and a contralateral skin site (i.e., control site). The signal intensity from the
tumor was always significantly higher than that from the contralateral site. Trends in results between the two methods were consistent with
tumor distribution increasing in a molecular weight-dependent manner (10 < 20 < 30 ≪ 40 ≪ 60 kDa). The 10 kDa nanocarrier was not detected in
tumors at 24 h, whereas 40-60 kDa nanocarriers were detected in
tumors for up to 96 h. The 30, 40, and 60 kDa nanocarriers showed 2.1, 5.3, and 4.1 times higher passive distribution in
tumors at 24 h, respectively, as compared to the 20 kDa nanocarrier. The 60 kDa nanocarrier exhibited 1.5 times higher
tumor distribution than 40 kDa nanocarrier at 96 h. Thus, PEG nanocarriers (40 and 60 kDa) with molecular weights close to or above the renal exclusion limit, which for globular
proteins is ≥45 kDa, showed significantly higher
tumor distribution than those below it. The hydrodynamic radii of PEG
polymers, measured using dynamic light scattering (DLS), showed that nanocarriers obtained from
polymers with hydrodynamic radii ≥8 nm exhibited higher
tumor distribution. Ex vivo mass balance studies revealed that nanocarrier tissue distribution followed the rank order
tumor > lung > spleen > liver > kidney > muscle > heart, thus validating the in vivo studies. The results of the current studies suggest that noninvasive dermal imaging of
tumors provides a reliable and rapid method for the initial screening of nanocarrier
tumor distribution pharmacokinetics.