Heparin-like sulfated
polysaccharides are potential
drug candidates owing to their ability to interact with angiogenic factors and inhibit angiogenesis,
tumor growth, and
metastasis. This study aimed to improve the delivery of
heparin-like anticancer
polysaccharides for accumulation at the
tumor site. We designed a nanocarrier system using
protamine attached to
polyethylene glycol (PEG) and evaluated the stability,
tumor targeting, and
tumor growth inhibition of the nanocarrier loaded with
heparin derivatives. When mixed with various polyanionic
heparin derivatives, the polycationic PEG-
protamine formed stable self-assembled nanocomplexes via ionic interactions, with flexible PEG chains located on the outside. Among the complexes, a nanocomplex loaded with a
low-molecular-weight heparin-
suramin conjugate (LHsura) had the most suitable average size (101.9nm) for the enhanced permeability and retention effect and allowed accumulation of LHsura at the
tumor site for up to 48h. In a
tumor-bearing mouse model, the PEG-
protamine and LHsura nanocomplex (10mg/kg/3days, intravenously), which could be extravasated through the
tumor vasculature, significantly inhibited
tumor growth, more than LHsura alone did. Overall, the self-assembled nanocomplexation of PEG-
protamine and LHsura helped control the release and extravasation of LHsura, which resulted in an antitumor effect on the target
tumor cells.