Human serum albumin (HSA) accumulates in
tumors by the enhanced permeability and retention (EPR) effect, which is a passive targeting effect in
tumors. A recent study showed that secreted
protein acidic and rich in
cysteine (SPARC), an
albumin-
binding protein, mediates
albumin accumulation in
tumors.
Arg-Gly-Asp (RGD) is a
peptide targeting
integrin αvβ3, which is highly expressed during
tumor angiogenesis. We investigated whether conjugation of RGD to HSA could synergistically enhance
tumor targeting. Accumulation of cRGDyK-HSA in
integrin αvβ3-expressing SK-OV3 cells was observed by confocal microscopy. In SK-OV3 cells overexpressing the
albumin binding protein SPARC, cellular uptake of HSA increased, but uptake of cRGDyK-HSA did not. cRGDyK-HSA showed decreased
tumor accumulation compared with HSA by positron emission tomography (PET) scanning and biodistribution studies in an SK-OV3 xenograft mouse model. In SK-OV3
tumors, HSA accumulation colocalized with SPARC expression, while cRGDyK-HSA only accumulated in the outer region of the
tumor, even though SPARC and
integrin αvβ3 were expressed within the
tumor core. We speculate that cRGDyK conjugation to HSA changes the characteristics of HSA and hinders its
tumor-targeting effect. Therefore, HSA should be modified to preserve its native characteristics and enhance the
tumor-targeting effects of HSA conjugates.