Click chemistry-based novel albumin nanoparticles for anticancer treatment via H2O2 generation

Abstract

Glucose oxidase (GOD) exerts anticancer effects by producing hydrogen peroxide (H2O2). However, the use of GOD is limited by its short half-life and low stability. Systemic H2O2 production following systemic absorption of GOD can also cause serious toxicity. GOD-conjugated bovine serum albumin nanoparticles (GOD-BSA NPs) may be useful for overcoming these limitations. Here, bioorthogonal copper-free click chemistry was employed to develop GOD-BSA NPs that are non-toxic and biodegradable and can effectively and rapidly conjugate proteins. These NPs retained their activity, unlike conventional albumin NPs. NPs using dibenzyl cyclooctyne (DBCO)-modified albumin, azide-modified albumin, and azide-modified GOD were fabricated in 10 min. After intratumoral administration, GOD-BSA NPs remained in the tumor for a longer period and displayed better anticancer activity than the effects of GOD alone. GOD-BSA NPs were approximately 240 nm in size and inhibited tumor growth to 40 mm3, whereas tumors treated with phosphate-buffered saline or albumin NPs had sizes of 1673 and 1578 mm3, respectively. GOD-BSA NPs prepared using click chemistry may be useful as a drug delivery system for protein enzymes.