Size- and pathotropism-driven targeting and washout-resistant effects of boronic acid-rich protein nanoparticles for liver cancer regression

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40nm-sized boronic acid-rich protein nanoparticles composed of bovine serum albumin and poly(N-3-acrylamidophenylboronic acid) were prepared by polymerizing N-3-acrylamidophenylboronic acid in the presence of albumin. The content of boronic acid-containing poly(N-3-acrylamidophenylboronic acid) in the nanoparticles can be tuned from 80% to 32% at constant nanoparticle size. When used to deliver doxorubicin in vivo, such sized nanoparticles show dominantly liver-targeting, and significant washout-resistant ability compared to those boronic acid-absent nanoparticles due to the interaction between sialic acid residues in the liver and boronic acid groups in the nanoparticles. The sialic acid overexpression on hepatic H22 tumor cells is demonstrated to be much higher than that on hepatocytes, resulting in the preferential accumulation of boronic acid-rich nanoparticles in liver cancer cells. In vivo antitumor examination in orthotopic liver cancer model shows that these doxorubicin-loaded nanoparticles not only have significantly superior ability in impeding tumor growth, but also induce distinct tumor regression with no hepatic and cardiac toxicities.