Near-infrared light and glucose dual-responsive cascading hydroxyl radical generation for in situ gelation and effective breast cancer treatment

• Published in: Biomaterials Vol. 228; p. 119568
• Main Authors: Hao, Yu, Dong, Ziliang, Chen, Muchao, Chao, Yu, Liu, Zhuang, Feng, Liangzhu, Hao, Y., Dong, Z.L., Chen, M.C., Chao, Y., Liu, Z., Feng, L.Z.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2020
• Subjects: Breast Neoplasms - drug therapy; Cascade production of OH; Chemodynamic therapy; Glucose; Glucose Oxidase; Humans; Hydroxyl Radical; Hyperthermia, Induced; In situ dual responsive gelation; NIR and glucose dual-responsive; Starvation therapy; Cascade production of OH; Starvation therapy; NIR and glucose dual-responsive; Chemodynamic therapy; In situ dual responsive gelation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2019.119568

A general therapeutic strategy to treat breast cancer is attractive as different subtypes of breast cancers often exhibit distinct response to existing cancer therapeutics. To this end, we prepare a catalyst couple of glucose oxidase (GOx) and gallic acid-ferrous (GA-Fe) nanocomplexes, a type of near-infrared (NIR) absorbing Fenton catalyst, to enable NIR-trigger in-situ gelation and enhanced chemodynamic/starvation therapy that appears to be effective for different types of breast cancer cells. In this system, GOx is mixed with GA-Fe in a solution of N,N-dimethylacrylamide (DMAA) and poly (ethylene glycol) double acrylate (PEGDA). Upon intratumoral injection and NIR laser exposure, such GA-Fe show rapid temperature increase, which would simultaneously increase the catalytic efficiencies of GA-Fe and GOx. The cascade production of hydroxyl radicals (•OH) from glucose is then initiated to enable polymerization of DMAA and PEGDA to form a hydrogel at the injection site within the tumor. The continuous production of cytotoxic •OH together with glucose depletion by the intratumorally fixed catalyst couple would further confer effective destruction of breast cancer tumors by such chemodynamic/starvation therapy. Our work presents a hydrogel-based therapeutic strategy for local treatment of solid tumors with high tumor destruction efficacy and low systemic toxicity.