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

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.