Multifunctional Polymeric Micelles with Amplified Fenton Reaction for Tumor Ablation

摘要

Relative to normal cells, tumor cells lack adequate capability of reactive oxygen scavenging. Thus, tumor cells can be selectively killed by increasing the concentration of reactive oxygen species in tumor tissue. In this report, we construct an integrated multifunctional polymeric nanoparticle which can selectively improve hydrogen peroxide (H2O2) levels in tumor tissue and convert them into more active hydroxyl radicals by Fenton reaction. First, the diblock copolymers containing polyethylene glycol (PEG) and poly(glutamic acid) modified by beta-cydodextrin (beta-CD) were synthesized. The block copolymer, ferrocenecarboxylic acid hexadecyl ester (DFc), and ascorbyl palmitate (PA) were coassembled in aqueous solution to obtain stable core shell micelles through the inclusion complexation between beta-CD moieties in the block copolymer and ferrocene (Fc) groups from DFc. After intravenous injection, the particles achieved significant accumulation in tumor tissue where ascorbic acid at the pharmacological concentration promotes the production of H2O2, and subsequently Fenton reaction was catalyzed by Fc groups to produce hydroxyl radicals to efficiently kill cancer cells and suppress tumor growth. The micellar systems possess great potentials toward cancer therapy through synergistic H2O2 production and conversion into hydroxyl radicals specifically in tumor tissue.